3. EL HIPERPARATIROIDISMO PRIMARIO ES UNA ENTIDAD CARACTERIZADA POR HIPERCALCEMIA ATRIBUIBLE A UNA SECRECIÓN AUTÓNOMA Y EXCESIVA DE PARATHORMONA HIPERPARATIROIDISMO PRIMARIO DEFINICIÓN AACE/AAES Position Statement, Endocr Pract. 2005;11(No. 1)
4.
5. SANGRE CELULA PARATIROIDEA REGULACION DEL METABOLISMO DEL CALCIO AUMENTO REABSORCION DE CALCIO SINTESIS 1-25 OH VITAMINA D AUMENTO RESORCION OSEA AUMENTO ABSORCION INTESTINAL DE CALCIO MODIFICADO – NEJM- Volume 343 Number 25 CALCIO
6. RECEPTOR SENSOR DE CALCIO VESICULA DE PTH CELULA PRINCIPAL RECEPTOR SENSOR DE CALCIO
7. DISTRIBUCION DEL CALCIO EN EL PLASMAA CALCIO UNIDO A PROTEÍNAS (40%) ALBUMINA 80% GLOBULINA 20% CALCIO LIBRE IÓNICO (50%) FORMANDO COMPLEJOS (10%) CALCIO TOTAL CALCIO IONICO SULFATO CITRATO LACTATO
10. INCIDENCIA HPPT SEGÚN SEXO Y EDAD MUJERES VARONES S W I S S M E D W K LY 2 0 0 9 ; 1 3 9 ( 2 7 – 2 8 ) : 4 0 0 – 4 0 4 Hospitalizacion media anual de pactes. con HPPT-1º x 100.000 hab. En Suiza 2000-2004
11. HPPT Asintomatico - Review - Clinical Endocrinology (2008) 58 , 155–164 EPIDEMIOLOGÍA 12.000 X AÑO CIRUGIA (USA) 1,5% > 65 AÑOS (USA) 3/1000 PREVALENCIA POBLACION GENERAL 21/1000 PREVALENCIA EN MUJERES POSMENOPAUSIA 20/100.000 INCIDENCIA ANUAL
12.
13. HIPERPARATIROIDISMO PRIMARIO INCIDENCIA -AUMENTO DE LA INCIDENCIA EN ULTIMOS AÑOS -16/100000 EN 1974 A 112/100000 EN 1992 (20/100000 EN 2002) - DETECCCION RUTINARIA DE CALCIO -CAMBIOS EN LA FORMA DE PRESENTACION AL DIAGNOSTICO -ANTES LITIASIS Y ENFERMEDAD OSEA Y AHORA ASINTOMATICO
16. N Engl J Med 1966 - 274:1174 Heath, H III, et al, N Engl J Med 1980 - 302:189 Silverberg, SJ, et al, - Am J Med 1990; 89:327. CAMBIOS EN LA PRESENTACION DEL HPPT LITIASIS RENAL ENFERMEDAD OSEA ASINTOMATICO
17.
18. HIPERCALCEMIA Leve o Moderada Intermitente A veces requiere multiples determinaciones ENFERMEDAD OSEA LITIASIS RENAL SINTOMAS Y SIGNOS POR EXCESO DE PTH SINTOMAS Y SIGNOS POR HIPERCALCEMIA ANOREXIA NAUSEAS CONSTIPACION POLIURIA POLIDIPSIA
30. GRADO DE HIPERCALCEMIA 8,5 A 10,5 mg % NORMAL 10,5 A 12 mg% LEVE 12 A 14 mg% MODERADA > 14 mg% CRITICA
31.
32. LABORATORIO CREATININA ELEVADA (INSUFICIENCIA RENAL) EN CASOS DE HPPT SEVERO HPPT MODERADO NO PRODUCE IRC HIPOFOSFATEMIA FOSFATO BAJO O NORMAL BAJO PTH INHIBE REABSORCION TUBULAR DE FOSFATO AUMENTO EXCRECION DE FOSFATO ESTADO ACIDO BASE ACIDOSIS METABOLICA LEVE PTH INHIBE REABSORCION TUBULAR DE BICARBONATO HIPERCALCEMIA > REABSORCION TUBULAR DE BICARBONATO ALCALIS LIBERADOS POR REABSORCION OSEA ANEMIA NORMOCITICA NORMOCROMICA RESPONDE A CIRUGIA PARATIROIDEA FIBROSIS DE LA MEDULA OSEA
42. SINDROMES ENDOCRINOS MULTIPLES Australian Family Physician Vol. 36, No. 12, December 2007 AUT. DOM. AUT. DOM. HERENCIA RET MENINA GEN MUTADO X FEOCROMOCITOMA X CA. MEDULAR TIROIDES X ADENOMA HIPOFISARIO X TUMORES PANCREATICOS X (35%) X (95%) HIPERPARATIROIDISMO MEN-2 MEN-1 HECHOS CLINICOS
47. HIPERCALCEMIA PTH CALCIURIA PTH BAJA (<20 pg/ml) HIPERCALCEMA NO MEDIADA POR PTH HPPT-1º PTH ALTA CALCIURIA <200 mg/24hs HPPT+< VIT D FHH PTH ALTA O NORMAL ALTA CALCIURIA > 200 mg/24hs
51. The Endocrinologist • Volume 17, Number 1, February 2007 Hyperparathyroidism LOCALIZACION PREQUIRURGICA COMPARACION ENTRE DIFERENTES METODOS - SOLOS Y COMBINADOS - 84 pactes
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53.
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55.
56. Brandon j. y col - Arch Intern Med. 2000;160:2161-2166 EFECTOS DE LA TERAPIA DE REMPLAZO HORMONAL (THR) SOBRE DENSIDAD OSEA EN MUJERES POSMENOPAUSICAS CON HPPT 1º SEGUIMIENTO A 4 AÑOS Y COMPARACION CON MUJERES SANAS POSMENOPAUSICAS 23 MUJERES POSTMENOPAUSICAS CON HPPT-1º 11 CON THR – 12 CON PLACEBO Vs 50 NORMALES POSTMENOP RESULTADOS DMO(4 AÑOS): COLUMNA VERTEBRAL= > 7,5% ANTEBRAZO= > 7% CUELLO FEMORAL= > 8,2% MARCADORES BIOQ. RECAMBIO OSEO BAJOS EN THR DENSIDAD OSEA PLACEBO Vs CONTROL SANO ANTEBRAZO COLUMNA VERTEBRAL 7% 7,5%
57.
58. 40 MUJERES POST MENOPAUSICAS CON HPPT 1º (EDAD= 70) ALENDRONATO 10 mg/dia O PLACEBO X 48 SEMANAS SUSPENSION X 24 SEMANAS JCEM February 2003, 88(2):581–587 Chow et al . • Alendronate in Primary Hyperparathyroidism ALENDRONATO EN HPPT PRIMARIO PLACEBO ALENDRONATO S/C OSTEOCALCINA 4,9 UI/lt 21,1 UI/lt FOSFATASA ALCALINA OSEA 0,01 mmol/lt 0,09 mmol/lt CALCIO SERICO 0,19% 3,79% DMO COLUMNA VERTEBRAL 0,25% 4,17 % DMO CUELLO FEMORAL
59. DENSIDAD OSEA DENSIDAD OSEA CUELLO FEMORAL COLUMNA VERTEBRAL CALCIO - PTH DENSIDAD OSEA JCEM February 2003, 88(2):581–587 Chow et al . • Alendronate in Primary Hyperparathyroidism ALENDRONATO EN HPPT PRIMARIO
60. DISEÑO: RANDOMIZADO DOBLE CIEGO, PLACEBO CONTROLADO POBLACIÓN: 44 PACIENTES CON HPTP-1º CON HIPERCALCEMIA < 12MG/DL INTERVENCIÓN: - ALENDRONATO/ALENDRONATO A (24 MESES) - PLACEBO X 12 MESES + ALENDRONATO 12 MESES (10MG) AUMENTO DENSIDAD OSEA Khan et al. • Alendronate in Primary Hyperparathyroidism J Clin Endocrinol Metab, July 2004, 89(7):3319–3325
61. ALENDRONATO EN HIPERPARATIROIDISMO CAMBIOS EN DENSIDAD OSEA Khan et al. • Alendronate in Primary Hyperparathyroidism J Clin Endocrinol Metab, July 2004, 89(7):3319–3325 COLUMNA VERTEBRAL CUELLO FEMORAL
62. DMO – COLUMNA LUMBAR DENSIDAD OSEA Y ALENDRONATO EN HPPT Arq Bras Endocrinol Metab vol 50 nº 4 Agosto 2006
63.
64. Rubin y col - J Clin Endocrinol Metab 88: 1174–1178, 2003 RALOXIFENO REDUCE CALCIO Y MARCADORES OSEOS EN MUJERES POSMENOPAUSICAS CON HPPT-1º RALOXIFENO RALOXIFENO ES AGONISTA ESTROGENICO SOBRE HUESO Y LIPIDOS Y ANTAGONISTA SOBRE UTERO Y MAMA
65.
66.
67.
68.
69. PLACEBO CINACALCET 30mg CINACALCET 40 mg CINACALCET 50 mg CINACALCET Y DESCENSO DE CALCIO – 1º DIA DE TRATAMIENTO J Clin Endocrinol Metab, December 2003, 88(12):5644–5649 Shoback et al. • Cinacalcet in Primary Hyperparathyroidism
70. PLACEBO CINACALCET 30mg CINACALCET 40 mg CINACALCET 50 mg CINACALCET Y DESCENSO DE CALCIO LUEGO DE 15 DIAS J Clin Endocrinol Metab, December 2003, 88(12):5644–5649 Shoback et al. • Cinacalcet in Primary Hyperparathyroidism
71. PLACEBO CINACALCET 30mg CINACALCET 40 mg CINACALCET 50 mg CINACALCET Y DESCENSO DE PTH – 1º DIA DE TRATAMIENTO J Clin Endocrinol Metab, December 2003, 88(12):5644–5649 Shoback et al. • Cinacalcet in Primary Hyperparathyroidism
72. J Clin Endocrinol Metab, January 2005, 90(1):135–141 Peacock et al. • Cinacalcet for Primary Hyperparathyroidism TRATAMIENTO CON CINACALCET
73. TRATAMIENTO CON CINACALCET J Clin Endocrinol Metab, January 2005, 90(1):135–141 Peacock et al. • Cinacalcet for Primary Hyperparathyroidism
77. METP – MUJER – 59 AÑOS DIC-08: ES DERIVADA A ENDOCRINOLOGO - PERSISTE DOLOR EN CUELLO Y NO REFIERE OTROS SINTOMAS TRAE 1-) ECOGRAFIA CUELLO = CON 2 NODULOS SOLIDOS HIPOECOS, NO HOMOGENEOS BIEN DELIMITADOS DE 11x6 Y OTRA DE 24x17 COMPATIBLES CON IMAGEN PARATIROIDEA (RICA VASCULARIZACION AL DOPLER) 2-) DENSITOMETRIA OSEA (2007) SOLICITADA POR GINECOLOGO CON SEVERA OSTEOPOROSIS
78. METP – MUJER – 59 AÑOS DIC-08: ES DERIVADA A ENDOCRINOLOGO - PERSISTE DOLOR EN CUELLO Y NO REFIERE OTROS SINTOMAS TRAE 1-) ECOGRAFIA CUELLO = CON 2 NODULOS SOLIDOS HIPOECOS, NO HOMOGENEOS BIEN DELIMITADOS DE 11X6 Y OTRA DE 24X17 COMPATIBLES CON IMAGEN PARATIROIDEA (RICA VASCULARIZACION AL DOPLER) 2-) DENSITOMETRIA OSEA (2007) SOLICITADA POR GINECOLOGO CON SEVERA OSTEOPOROSIS
PTH מורכב מ -84 ח &quot; א , אך החלק האקטיבי הוא 34 הח . הראשונות , המסומנות בצהוב . חומצות אמינו 1-6 ב PTH הן אלו הדרושות להפעלת הרצפטור . אנאלוגים 7-34 יכולים להיקשר לרצפטור אך לא מפעילים אותו . משמשים לכם כ competitive antagosints . האתר הדרוש לקישור הנו 18-34
Figure 1. The Parathyroid Axis. The synthesis of parathyroid hormone (PTH) and parathyroid hormone–related peptide (PTHrP) is shown on the left, and their target sites of action are shown on the right. Both act by means of the same receptor (also termed the type 1 PTH receptor). Negative feedback of 1,25-dihydroxyvitamin D is not shown. See the text for further descriptions. An excess or deficiency of parathyroid hormone may be treated either at the level of parathyroid hormone release (and the parathyroid hormone receptors) or at selected sites distal to the parathyroid hormone receptors. Blue arrows indicate extracellular calcium flow.
קלציום משפיע על הפרשת ה - PTH ע &quot; י ה - CSR ( Ca sensing receptor , סוג של GPCR ) – בהיפרקלצמיה הוא משתק הפרשת PTH מהבלוטה , וכאשר יש היפוקלצמיה , השיתוק נעלם .
Fig. 1. Relationship between intact parathyroid hormone ( iPTH ) and ionized calcium in normal physiologic state and hyperparathyroidism. Shaded area = normal range for ionized calcium.
INCIDENCIA ANNUAL 20/100000 PREVALENCIA EN MUJERES POSMENOPASICAS The annual incidence of PHPT was estimated to be approximately 20 per 100 000,with a prevalence in postmenopausal women of 21 in 1000, which is equivalent to 3 in 1000 in the general population. Although in the USA PHPT might be present in more than 1·5% of people aged 65 years or older, representing several million people,surgery for PHPT is only performed on approximately 12 000 patients per year. It appears, therefore, that the majority of patients remain undiagnosed or untreated(5) during a 10-year follow-up of 121 patients with PHPT,14 of 52 asymptomatic patients who were not offered surgery had progression of disease and developed at least one new indication for parathyroidectomy (5)
Biochemical screening tests that include measurements of serum calcium currently account for the identification of at least 80 percent of patients with primary hyperparathyroidism in western countries (show figure 1) [4]. These patients are usually asymptomatic and have mild and often intermittent hypercalcemia [5,6]. In most asymptomatic patients, the mean serum calcium concentration is less than 1.0 mg/dL (0.25 mmol/L) above the upper limit of the normal range [5]. Occasionally, patients are normocalcemic, and elevated parathyroid hormone levels are detected through a work-up of low bone density [7]. This entity, termed normocalcemic hyperparathyroidism, is discussed elsewhere. (See &quot;Diagnosis and differential diagnosis of primary hyperparathyroidism&quot; section on Normocalcemic primary hyperparathyroidism versus secondary hyperparathyroidism). Some patients with presumed asymptomatic hyperparathyroidism, when carefully questioned, have nonspecific symptoms, such as fatigue, weakness, anorexia, mild depression, and mild cognitive or neuromuscular dysfunction, and others simply miss work often [8-11]. With time, patients with true asymptomatic hyperparathyroidism may develop clinical manifestations of hyperparathyroidism, including skeletal manifestations, nephrocalcinosis, or kidney stones. Thus, the differentiation between symptomatic and asymptomatic primary hyperparathyroidism is not always clear-cut
Different patterns of presentation of primary hyperparathyroidism in three different time periods. The latest survey shows that 80 percent of patients are asymptomatic and discovered incidentally on routine blood screening; bone disease, on the other hand, has virtually disappeared as a presenting symptom. Bone disease was assessed by x-rays and bone scans; patients with skeletal involvement by bone density measurement were not included. Data from Cope, O, N Engl J Med 1966; 274:1174; Heath, H III, et al, N Engl J Med 1980; 302:189; and Silverberg, SJ, et al, Am J Med 1990; 89:327.
Measurement of serum calcium — A single elevated serum calcium concentration should be repeated to confirm the presence of hypercalcemia. The total serum calcium concentration should be used for both the initial and the repeat serum calcium measurements. If a laboratory known to measure ionized calcium reliably is available, some authorities prefer to measure the ionized calcium, although this usually adds little in patients with normal serum albumin concentrations and no abnormalities in acid base balance Diagnosis is made by documenting hypercalcaemia in the presence of an elevated or inappropriately ‘normal’ serum PTH level, and a fractional urinary excretion of calcium >0.02.3 The fractional excretion of calcium is calculated as (urine calcium x serum creatinine) ÷ (serum calcium x urine creatinine).
Measurement of serum calcium — A single elevated serum calcium concentration should be repeated to confirm the presence of hypercalcemia. The total serum calcium concentration should be used for both the initial and the repeat serum calcium measurements. If a laboratory known to measure ionized calcium reliably is available, some authorities prefer to measure the ionized calcium, although this usually adds little in patients with normal serum albumin concentrations and no abnormalities in acid base balance Diagnosis is made by documenting hypercalcaemia in the presence of an elevated or inappropriately ‘normal’ serum PTH level, and a fractional urinary excretion of calcium >0.02.3 The fractional excretion of calcium is calculated as (urine calcium x serum creatinine) ÷ (serum calcium x urine creatinine).
Measurement of serum calcium — A single elevated serum calcium concentration should be repeated to confirm the presence of hypercalcemia. The total serum calcium concentration should be used for both the initial and the repeat serum calcium measurements. If a laboratory known to measure ionized calcium reliably is available, some authorities prefer to measure the ionized calcium, although this usually adds little in patients with normal serum albumin concentrations and no abnormalities in acid base balance Diagnosis is made by documenting hypercalcaemia in the presence of an elevated or inappropriately ‘normal’ serum PTH level, and a fractional urinary excretion of calcium >0.02.3 The fractional excretion of calcium is calculated as (urine calcium x serum creatinine) ÷ (serum calcium x urine creatinine).
LABORATORY FINDINGS — The diagnosis of hyperparathyroidism is usually first suspected by the finding of an elevated serum calcium concentration. A frankly elevated PTH concentration or a PTH value in the upper half of the normal range in the setting of hypercalcemia is likely the result of primary hyperparathyroidism. Renal insufficiency — The development of renal insufficiency in primary hyperparathyroidism is related to the degree and duration of hypercalcemia. Mild hypercalcemia is rarely associated with renal insufficiency. (2) Hypophosphatemia — In most patients are in the lower half of the normal range. PTH inhibits the proximal tubular reabsorption of phosphate, leading to increased phosphate excretion. Magnesium balance — Renal tubular reabsorption of magnesium is stimulated by PTH but inhibited by hypercalcemia. Overall, magnesium excretion tends to be slightly increased, and a few patients have mild hypomagnesemia. Acid-base balance — High concentrations of PTH inhibit proximal tubular bicarbonate reabsorption, which tends to cause a mild metabolic acidosis. However, this effect is usually counterbalanced by the alkali liberated as a result of increases in bone resorption and in tubular reabsorption of bicarbonate caused by hypercalcemia. Thus, metabolic acidosis is unusual in primary hyperparathyroidism unless serum PTH concentrations are very high or the patient has coexistent renal insufficiency Anemia — Patients with severe hyperparathyroidism may have a normochromic normocytic anemia that responds to parathyroidectomy . The mechanism is unclear, but marrow fibrosis may be important (2)
Bone mineral density — Patients with hyperparathyroidism may have decreased bone mineral density (BMD), in particular at more cortical sites (forearm and hip) as compared with more cancellous sites (spine). Randomized trials have demonstrated increased BMD following parathyroidectomy. Measurement of BMD is an essential part of the management of the disease, The degree of bone loss is reflective of the severity of hyperparathyroidism and is useful for making recommendations for parathyroid surgery or observation with monitoring – Up to Date 2009
Fig. 3— 44-year-old woman with hyperparathyroidism due to right inferior parathyroid adenoma. Resected gland weighed 629 mg, nearly 15 times weight of a normal gland (40–50 mg). A, Sonogram shows typical hypoechoic adenoma ( arrows ) deep in relation to lower pole of thyroid. B, Color Doppler sonogram shows peripheral feeding vessel ( arrow ) characteristic of parathyroid adenomas. Also note typical arc or rim vascularity.
Tc SESTAMIBI scan left parathyroid tracer uptake
Patients without an apparent secondary cause may have a &quot;forme fruste&quot; of primary hyperparathyroidism. in the natural history of primary hyperparathyroidism, elevated PTH levels would precede the development of overt hypercalcemia In one prospective study of 37 patients with normocalcemic hyperparathyroidism, 41 percent developed evidence for progressive hyperparathyroid disease during a median of three years(3)
Among such patients, the majority are women over age 50 years most have few if any symptoms the distinction between asymptomatic and symptomatic PHPT is not always clear-cut the primary goal is to identify the asymptomatic individuals at risk for disease progression who have features of the disease that may improve following parathyroidectomy the risks and benefits of medical versus surgical management in this population. (4)
Familial hypocalciuric hypercalcemia — Familial hypocalciuric hypercalcemia (FHH) is due to an inactivating mutation in the calcium-sensing receptor in the parathyroid glands and the kidneys A family history of hypercalcemia, especially in young children, and the absence of symptoms and signs of hypercalcemia (such as anorexia, neuromuscular symptoms, and polyuria) are characteristic of this disorder. Fifteen to 20 percent of patients with FHH may have a mildly elevated PTH concentration In these individuals, it may be difficult to distinguish asymptomatic primary Hyperparathyroidism from FHH. It is important to make this distinction, however, because FHH is a benign inherited condition that typically does not require parathyroidectomy, nor will it be cured by it. The major feature that distinguishes FHH from primary hyperparathyroidism (PHPT) is a low urine calcium excretion and Ca/Cr clearance ratio (show table 2). In contrast, most patients with primary hyperparathyroidism have either normal or elevated urinary calcium excretion. (3) patients who have familial hypocalciuric hypercalcemia. Patients with this disorder have mild hypercalcemia, few if any symptoms, no evidence of end organ damage from their disease, and no benefit from parathyroidectomy. (
— Secondary hyperparathyroidism occurs when the parathyroid gland appropriately responds to a reduced level of extracellular calcium. PTH concentrations rise, and calcium is mobilized by increasing intestinal absorption (via increase in calcitriol) and by increasing bone resorption. Thus, it is characterized biochemically by elevated PTH and normal or low serum calcium concentrations Secondary hyperparathyroidism may occur in patients with renal failure and impaired calcitriol (1,25 dihydroxyvitamin D) production, as well as in individuals with inadequate calcium intake or absorption, as can occur with vitamin D deficiency or with gastrointestinal diseases causing malabsorption (show table 3). Assessment of renal function (serum creatinine), vitamin D status (25-hydroxyvitamin D, 25OHD), and calcium sufficiency (urinary calcium excretion) may help differentiate normocalcemic primary and secondary hyperparathyroidism
Malignancy — Primary hyperparathyroidism (PHPT) and malignancy are the most common causes of hypercalcemia, accounting for more than 90 percent of cases It is usually not difficult to differentiate between them. Malignancy is often evident clinically by the time it causes hypercalcemia, and patients with hypercalcemia of malignancy have higher calcium concentrations and are more symptomatic from hypercalcemia than individuals with primary hyperparathyroidism Intact PTH concentrations are generally undetectable or very low in hypercalcemia of malignancy and are elevated or high-normal in PHPT
Figure 2. Serum Calcium and Parathyroid Hormone Concentrations in Patients with Hypercalcemia and Hypocalcemia Due to Various Causes. The diagnosis of a serious mineral disorder is usually clear, as illustrated by the nonoverlapping domains in the figure, but in the early stages of these disorders, the values for either serum calcium or parathyroid hormone may overlap with the normal ranges. The following diagnoses are not shown: familial hypocalciuric hypercalcemia (midpoint of the range for serum calcium, 11.5 mg per deciliter, and for serum parathyroid hormone, 30 pg per milliliter); neonatal severe primary hyperparathyroidism (midpoint for serum calcium, 18 mg per deciliter, and for serum parathyroid hormone, 500 pg per milliliter); hypercalciuric hypocalcemia (midpoint for serum calcium, 7 mg per deciliter, and for serum parathyroid hormone, 10 pg per milliliter); tertiary uremic hyperparathyroidism (midpoint for serum calcium, 11 mg per deciliter, and for serum parathyroid hormone, 2000 pg per milliliter); tertiary hyperparathyroidism after renal transplantation that corrected uremia (midpoint for serum calcium, 12 mg per deciliter, and for serum parathyroid hormone, 200 pg per milliliter); and adynamic bone disease with uremia (midpoint for serum calcium, 9 mg per deciliter, and for serum parathyroid hormone, 50 pg per milliliter). To convert values for serum calcium to millimoles per liter, multiply by 0.25, and to convert values for serum parathyroid hormone to picomoles per liter, multiply by 0.11.
concluded that surgery is indicated in asymptomatic patients who meet the following conditions Serum calcium concentration of 1.0 mg/dL or more above the upper limit of normal Creatinine clearance that is reduced to <60 mL/min Bone density at the hip, lumbar spine, or distal radius that is more than 2.5 standard deviations below peak bone mass (T score <-2.5) and/or previous fragility fracture Age less than 50 years
Operative management is currently the only curative therapy for patients with PHPT. Procedures such as percutaneous ethanol injection, laser therapy, and radio-frequency ablation are considered experimental at this point. Operative cure rates of 95 to 98% with complication rates of 1 to 2% are possible when parathyroidectomy is performed by experienced surgeons. Serious complications consist of recurrent laryngeal nerve injury, persistent or recurrent HPT, permanent hypoparathyroidism, and bleeding. Mortality from operative intervention is extremely low. The main causes of operative failures are multiglandular disease, ectopic or supernumerary parathyroid glands, parathyroid cancer, and surgical inexperience.
FIGURE 2. Sensitivity, specificity, positive predictive value (PPV) for single use of test and combined use of test, respectively. Planar Tc-99m-sesta-MIBI scintigraphy and sonography have a high sensitivity and positive predictive value for the detection of abnormal parathyroid glands in patients with evidence of hyperparathyroidism. The combination of the studies was better than either test alone. The anatomic resolution achieved with ultrasonography combined with the functional information gained from Tc-99m-sesta-MIBI scintigraphy provided the most effective approach for the localization of pathologically hyperfunctioning parathyroids. This combination of tests is recommended before first-time surgery in all cases of primary hyperparathyroidism, especially if a microinvasive approach is chosen. SPECT is useful in patients with ectopic lesions.
Preventive measures — A number of measures should be recommended to patients who do not undergo surgery, including the following: Avoid factors that can aggravate hypercalcemia, including thiazide diuretic and lithium carbonate therapy, volume depletion, prolonged bed rest or inactivity, and a high calcium diet (>1000 mg/day). Encourage physical activity to minimize bone resorption. Encourage adequate hydration (at least six to eight glasses of water per day) to minimize the risk of nephrolithiasis. Maintain a moderate calcium intake (1000 mg/day) A low calcium diet may lead to further increases in PTH secretion and could aggravate bone disease Maintain moderate vitamin D intake (400 to 600 int. units daily). (Vitamin D deficiency stimulates PTH secretion and bone resorption, and therefore is deleterious in patients with primary HPPT) (4) Preventive measures — A number of measures should be recommended to patients who do not undergo surgery, including the following: Avoid factors that can aggravate hypercalcemia, including thiazide diuretic and lithium carbonate therapy, volume depletion, prolonged bed rest or inactivity, and a high calcium diet (>1000 mg/day). Encourage physical activity to minimize bone resorption. Encourage adequate hydration (at least six to eight glasses of water per day) to minimize the risk of nephrolithiasis. Maintain a moderate calcium intake (1000 mg/day) A low calcium diet may lead to further increases in PTH secretion and could aggravate bone disease Maintain moderate vitamin D intake (400 to 600 int. units daily). (Vitamin D deficiency stimulates PTH secretion and bone resorption, and therefore is deleterious in patients with primary HPPT) (4)
Estrogen-progestin therapy — Estrogen-progestin therapy is beneficial in postmenopausal women with primary hyperparathyroidism because of its ability to reduce bone resorption. In two trials, serum calcium concentrations decreased by 0.5 to 1.0 mg/dL and bone density increased slightly However, there are significant risks associated with estrogen-progestin therapy, including increased risks of breast cancer, stroke, and coronary heart disease. Therefore, estrogen or estrogen-progestin therapy should not be a first-line therapy for women with primary hyperparathyroidism(4) bisphosphonates are recommended for the treatment of low bone mass in patients with hyperparathyroidism who are not candidates for surgery Raloxifene — Raloxifene, a selective estrogen receptor modulator is available in many countries for the prevention and treatment of osteoporosis. In a short-term study of 18 postmenopausal women with asymptomatic PHPT, raloxifene (60 mg/day for eight weeks) reduced mean serum calcium concentration by 0.4 mg/dL at a single time point (8 weeks) [67]. Further data are needed before recommending raloxifene for this indication(4) Calcimimetics — Calcimimetic agents activate the calcium-sensing receptor in the parathyroid gland, thereby inhibiting PTH secretion. One calcimimetic drug, cinacalcet, is now available in some countries for the treatment of secondary hyperparathyroidism associated with renal failure and for hypercalcemia in parathyroid cancer. Although not currently approved for use in primary hyperparathyroidism (PHPT), cinacalcet may normalize serum calcium in these patients. In a one-year trial of 78 patients with PHPT randomly assigned to cinacalcet or placebo , cinacalcet therapy normalized serum calcium in 73 percent of subjects compared with only 5 percent in the placebo group. Serum PTH concentrations decreased by 7.5 percent with cinacalcet, but increased in the placebo group. Thus, cinacalcet is not the medical equivalent of parathyroidectomy, because there is no improvement in BMD.
Estrogen-progestin therapy — Estrogen-progestin therapy is beneficial in postmenopausal women with primary hyperparathyroidism because of its ability to reduce bone resorption. In two trials, serum calcium concentrations decreased by 0.5 to 1.0 mg/dL and bone density increased slightly However, there are significant risks associated with estrogen-progestin therapy, including increased risks of breast cancer, stroke, and coronary heart disease. Therefore, estrogen or estrogen-progestin therapy should not be a first-line therapy for women with primary hyperparathyroidism(4) bisphosphonates are recommended for the treatment of low bone mass in patients with hyperparathyroidism who are not candidates for surgery Raloxifene — Raloxifene, a selective estrogen receptor modulator is available in many countries for the prevention and treatment of osteoporosis. In a short-term study of 18 postmenopausal women with asymptomatic PHPT, raloxifene (60 mg/day for eight weeks) reduced mean serum calcium concentration by 0.4 mg/dL at a single time point (8 weeks) [67]. Further data are needed before recommending raloxifene for this indication(4) Calcimimetics — Calcimimetic agents activate the calcium-sensing receptor in the parathyroid gland, thereby inhibiting PTH secretion. One calcimimetic drug, cinacalcet, is now available in some countries for the treatment of secondary hyperparathyroidism associated with renal failure and for hypercalcemia in parathyroid cancer. Although not currently approved for use in primary hyperparathyroidism (PHPT), cinacalcet may normalize serum calcium in these patients. In a one-year trial of 78 patients with PHPT randomly assigned to cinacalcet or placebo , cinacalcet therapy normalized serum calcium in 73 percent of subjects compared with only 5 percent in the placebo group. Serum PTH concentrations decreased by 7.5 percent with cinacalcet, but increased in the placebo group. Thus, cinacalcet is not the medical equivalent of parathyroidectomy, because there is no improvement in BMD.
Estrogen-progestin therapy — Estrogen-progestin therapy is beneficial in postmenopausal women with primary hyperparathyroidism because of its ability to reduce bone resorption. In two trials, serum calcium concentrations decreased by 0.5 to 1.0 mg/dL and bone density increased slightly However, there are significant risks associated with estrogen-progestin therapy, including increased risks of breast cancer, stroke, and coronary heart disease. Therefore, estrogen or estrogen-progestin therapy should not be a first-line therapy for women with primary hyperparathyroidism(4) bisphosphonates are recommended for the treatment of low bone mass in patients with hyperparathyroidism who are not candidates for surgery Raloxifene — Raloxifene, a selective estrogen receptor modulator is available in many countries for the prevention and treatment of osteoporosis. In a short-term study of 18 postmenopausal women with asymptomatic PHPT, raloxifene (60 mg/day for eight weeks) reduced mean serum calcium concentration by 0.4 mg/dL at a single time point (8 weeks) [67]. Further data are needed before recommending raloxifene for this indication(4) Calcimimetics — Calcimimetic agents activate the calcium-sensing receptor in the parathyroid gland, thereby inhibiting PTH secretion. One calcimimetic drug, cinacalcet, is now available in some countries for the treatment of secondary hyperparathyroidism associated with renal failure and for hypercalcemia in parathyroid cancer. Although not currently approved for use in primary hyperparathyroidism (PHPT), cinacalcet may normalize serum calcium in these patients. In a one-year trial of 78 patients with PHPT randomly assigned to cinacalcet or placebo , cinacalcet therapy normalized serum calcium in 73 percent of subjects compared with only 5 percent in the placebo group. Serum PTH concentrations decreased by 7.5 percent with cinacalcet, but increased in the placebo group. Thus, cinacalcet is not the medical equivalent of parathyroidectomy, because there is no improvement in BMD.
Estrogen-progestin therapy — Estrogen-progestin therapy is beneficial in postmenopausal women with primary hyperparathyroidism because of its ability to reduce bone resorption. In two trials, serum calcium concentrations decreased by 0.5 to 1.0 mg/dL and bone density increased slightly However, there are significant risks associated with estrogen-progestin therapy, including increased risks of breast cancer, stroke, and coronary heart disease. Therefore, estrogen or estrogen-progestin therapy should not be a first-line therapy for women with primary hyperparathyroidism(4) bisphosphonates are recommended for the treatment of low bone mass in patients with hyperparathyroidism who are not candidates for surgery Raloxifene — Raloxifene, a selective estrogen receptor modulator is available in many countries for the prevention and treatment of osteoporosis. In a short-term study of 18 postmenopausal women with asymptomatic PHPT, raloxifene (60 mg/day for eight weeks) reduced mean serum calcium concentration by 0.4 mg/dL at a single time point (8 weeks) [67]. Further data are needed before recommending raloxifene for this indication(4) Calcimimetics — Calcimimetic agents activate the calcium-sensing receptor in the parathyroid gland, thereby inhibiting PTH secretion. One calcimimetic drug, cinacalcet, is now available in some countries for the treatment of secondary hyperparathyroidism associated with renal failure and for hypercalcemia in parathyroid cancer. Although not currently approved for use in primary hyperparathyroidism (PHPT), cinacalcet may normalize serum calcium in these patients. In a one-year trial of 78 patients with PHPT randomly assigned to cinacalcet or placebo , cinacalcet therapy normalized serum calcium in 73 percent of subjects compared with only 5 percent in the placebo group. Serum PTH concentrations decreased by 7.5 percent with cinacalcet, but increased in the placebo group. Thus, cinacalcet is not the medical equivalent of parathyroidectomy, because there is no improvement in BMD.
Estrogen-progestin therapy — Estrogen-progestin therapy is beneficial in postmenopausal women with primary hyperparathyroidism because of its ability to reduce bone resorption. In two trials, serum calcium concentrations decreased by 0.5 to 1.0 mg/dL and bone density increased slightly However, there are significant risks associated with estrogen-progestin therapy, including increased risks of breast cancer, stroke, and coronary heart disease. Therefore, estrogen or estrogen-progestin therapy should not be a first-line therapy for women with primary hyperparathyroidism(4) bisphosphonates are recommended for the treatment of low bone mass in patients with hyperparathyroidism who are not candidates for surgery Raloxifene — Raloxifene, a selective estrogen receptor modulator is available in many countries for the prevention and treatment of osteoporosis. In a short-term study of 18 postmenopausal women with asymptomatic PHPT, raloxifene (60 mg/day for eight weeks) reduced mean serum calcium concentration by 0.4 mg/dL at a single time point (8 weeks) [67]. Further data are needed before recommending raloxifene for this indication(4) Calcimimetics — Calcimimetic agents activate the calcium-sensing receptor in the parathyroid gland, thereby inhibiting PTH secretion. One calcimimetic drug, cinacalcet, is now available in some countries for the treatment of secondary hyperparathyroidism associated with renal failure and for hypercalcemia in parathyroid cancer. Although not currently approved for use in primary hyperparathyroidism (PHPT), cinacalcet may normalize serum calcium in these patients. In a one-year trial of 78 patients with PHPT randomly assigned to cinacalcet or placebo , cinacalcet therapy normalized serum calcium in 73 percent of subjects compared with only 5 percent in the placebo group. Serum PTH concentrations decreased by 7.5 percent with cinacalcet, but increased in the placebo group. Thus, cinacalcet is not the medical equivalent of parathyroidectomy, because there is no improvement in BMD.
