Lecture 20 disorders of hypothalamus, pituitary and thyroid glands - Pathology

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Disorders of Hypothalamus, Pituitary & Thyroid glands
Lecture 20
Hypothalamus
 The hypothalamus is located in the middle of the base of the brain
 One of the most important functions of the hypothalamus is to link the nervous
system to the endocrine system via the pituitary gland (hypophysis).
 The pituitary gland : also known as the hypophysis,
 is a roundish organ that lie immediately beneath the hypothalamus
 resting in a depression of the base of the skull called the: sella turcica ("Turkish
saddle").
 It has the size and shape of a garbanzo bean.
 Through the production of hypothalamic releasing factors, the C.N.S. exerts a major
regulatory influence over pituitary hormone secretion.
 The hypothalamus acts upon the pituitary in two principal ways:
1) by the secretion of hormones or prohormones, which are transported to the posterior
pituitary
2) by the secretion of controlling hormones into the hypothalmic hypophyseal portal
veins
 (Portal veins are defined as veins between two capillary beds), a blood supply running
from the hypothalamus to the pituitary.
Pituitary gland
The pituitary gland is composed of two parts: anterior and posterior.
1) The anterior pituitary (adenohypophysis) is a classical gland composed predominantly
of cells that secrete protein hormones.
2) The posterior pituitary (neurohypophysis) is not really an organ, but an: extension of
the hypothalamus.

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 It is composed largely of the axons of hypothalamic neurons which extend
downward as a large bundle behind the anterior pituitary.
 It also forms the so-called pituitary stalk, which appears to suspend the anterior gland
from the hypothalamus.
Hypothalamic Hormones & their Effect on Pituitary

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Normal hypothalamic-pituitary-thyroid axis
 Thyrotropin-releasing hormone (TRH) from the hypothalamus stimulates TSH from the
pituitary, which stimulates thyroid hormone release.
 With an increase in either triiodothyronine (T3) or thyroxine (T4) there is feedback
inhibition of hypothalamic thyroid releasing hormone (TRH) and pituitary thyroid
stimulating hormone (TSH).
 Decreased TRH and TSH cause a decrease in T3 and T4. Reciprocally, with a decrease
in T3 or T4, there is an increase in TRH and TSH leading to an increased T3 and T4.
Thyroid gland Location

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 The thyroid is a bilobed gland connected by a narrow isthmus which lies anterior and
inferior to the larynx.
 The normal thyroid weighs about 35 grams.
The thyroid gland and the follicular structure
Thyroid Gland (Overview)
 The main functional unit of the thyroid, the follicle is lined by cuboidal to columnar
epithelium.
 The Pituitary gland produces TSH, which binds to follicle cell receptors. As a result:
 The follicle cells of the thyroid produce a glycoprotein called thyroglobulin.
 The major constituent of thyroglobulin is the amino acid Tyrosine
 Thyroglobulin is the thyroid hormone storage form.
 Thyroid peroxidase or thyroperoxidase (TPO) is an enzyme found in the thyroid follicle
cells and it is secreted into colloid.
 Unrelated to its physiology, but located within the thyroid, are parafollicular
concentrations of cells known as parafollicular or thyroid “C” cells.
 The parafollicular C cells secretes calcitonin and are involved with calcium homeostasis.
Major sources of iodine
 Thyroid hormones are unique biological molecules in that they incorporate iodine in their
structure.
 Thus, adequate iodine intake either through diet or water is required for normal thyroid
hormone production.
 Major sources of iodine are: - iodized salt - iodated bread - dairy products - shellfish
 Minimum requirement (RDA :Recommended Daily Allowance): 75 micrograms/day

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 Dietary iodine is absorbed in the GI tract, then taken up by the thyroid gland (or
removed from the body by the kidneys).
Thyroid hormone synthesis
 Iodide is actively taken up the thyroid cell;
 iodination of tyrosine residues in thyroglobulin results in formation of monoiodotyrosine (MIT)
and diiodotyrosine (DIT).
 When one MIT and one DIT couple→ triiodothyronine (T3).
 Two DITs couple to form→ thyroxine (T4).
 T4 and T3 are cleaved from thyroglobulin before secretion from the thyroid gland.
 TSH (secreted by the pituitary gland) stimulates all these reactions.
 Most thyroid hormone in the blood is bound to a thyroid binding protein (TBG).
 The unbound or free forms of T4 (0.04%) and T3 (0.4%) are the metabolically active
components of thyroid hormones.
 The thyroid gland secretes about 100nmol of T4 and only 5nmol of T3. In the peripheral
circulation about 35nmol of T4 is deiodinated to form T3.
 Although T3 is present in lower concentration than T4, T3 is 3 to 8 times more potent that
T4.
Function of thyroid peroxidase
 Synthesis of thyroid hormones requires iodine & thyroid peroxidase.
1. Iodine, ingested in food and water as iodide is converted to organic iodine
(organification) within follicular cells by thyroid peroxidase.
2. The follicular cells surround a space filled with colloid, which consists of thyroglobulin
(a glycoprotein containing tyrosine within its matrix). Tyrosine in contact with the
membrane of the follicular cells is iodinated at 1 (MIT; monoiodotyrosine) or 2 (DIT;
diiodotyrosine) sites by thyroid peroxidase.
3. and then coupled to produce the 2 forms of thyroid hormone (diiodotyrosine +
diiodotyrosine → T4; diiodotyrosine + monoiodotyrosine → T3) by thyroid peroxidase.

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Thyroid hormone Function: It promotes:
 Growth of the brain, muscle, kidneys, genitalia, pituitary gland, and skin.
 There is a general increase in bodily functions (i.e. increased heart rate, GI motility,
skeletal muscle contraction, etc.) and the generation of heat ( BMR).
o BMR (Basal Metabolic Rate): The amount of energy (in the form of calories) that
the body needs to function while resting for 24 hours.
 Thyroid hormone stimulates lipid and glucose synthesis.
 With increased beta-adrenergic stimulation and catecholamine release the patient
becomes irritable and nervous.
Acquired Hypothyroidism
 Primary hypothyroidism: is a decrease in thyroid function resulting from destruction or
dysfunction of the thyroid gland.
 Secondary hypothyroidism: represents or impaired hypothalamic or pituitary function
o Primary hypothyroidism is much more common than Secondary.
Causes of hypothyroidism:
1) Primary disorders:
Common (~ 95%)
 *Hashimoto's disease autoimmune thyroid destruction
 *Primary (atrophic) hypothyroidism (Probably end-stage Hashimoto's disease)
 Post-radioiodine therapy which destroys thyroid tissue ,
 Thyroidectomy (i.e., surgical removal )

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Uncommon (~ 5%)
 Thyroiditis (non-lymphocytic)
 Impaired T4 synthesis due to genetic defect ,
 Certain goitrogenic agents :
 lithium carbonate (i.e., used in the treatment of manic-depressive states) .
 Antithyroid drugs propylthiouracil and methimazole in continuous dosage can block
hormone synthesis and produce hypothyroidism with goiter.
 Iodine-containing drugs (e.g., kelp tablets, iodide-containing cough syrups,
radiographic contrast media) also can block thyroid hormone production, particularly
in persons with autoimmune thyroid disease.
 Amiodarone (an antiarrhythmic drug), which contains 75 mg of iodine per 200-mg
tablet, is being increasingly implicated in causing thyroid problems.
 Iodine deficiency, which can cause goiter and hypothyroidism, is rare in the United
States because of the widespread use of iodide salt and other iodide sources.
2) Secondary disorders:
May result from a loss of trophic stimulation due to damage or disease of the
hypothalamic-pituitary axis. Thus, in the absence of the TRH and/or TSH drive, thyroid
function is reduced. Due to:
 Hypopituitarism(~ 1%)caused by e.g. tumors, surgery, radiotherapy
 Impaired TSH synthesis
 Hypothalamic damage (~ <1%)due to tumors, radiotherapy or trauma
*Hashimoto’s thyroiditis:
 An autoimmune disorder in which the thyroid gland may be totally destroyed by an
immunologic process of unknown cause.
 It is the major cause of goiter and hypothyroidism in children and adolescents.
Hashimoto’s thyroiditis is predominantly a disease of women, with a female-to-male ratio
of 10:1 to 20:1.
 The goiter is the result of :
 Diffuse lymphocytic infiltration (which gives it a number of alternative names such
as chronic lymphocytic thyroiditis).
 TSH-stimulated hyperplasia of surviving thyroid tissue due to loss of feedback
inhibition from the thyroid hormones.
 The goiter is usually diffuse with a characteristic at least to the experienced clinician
'rubbery' feel to palpation. It is rare for it to be painful or problematic by its size and
surgery is infrequently required.
 Other features of this disease are Antibodies against TPO (enzyme thyroid peroxidase)
& thyroglobulin (usually in much higher titers than in Graves').

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 At the onset only a goiter may be present. In time, hypothyroidism usually becomes
evident.
 Although the disorder usually causes hypothyroidism, a hyperthyroid state may
develop midcourse in the disease. In which case it is termed 'Hashitoxicosis', but the
degree of hyperthyroidism is usually milder than in Graves' disease.
 The transient hyperthyroid state is caused by leakage of preformed thyroid hormone from
damaged cells of the gland.
*Primary (atrophic) hypothyroidism:
 Hypothyroidism associated with primary thyroid atrophy is termed primary myxedema.
 It seems highly likely that non-goitrous myxedema is simply an end-stage of
autoimmune destruction leaving only fibrous remnants.
 A role for antibodies to the TSH receptor that block the actions of TSH (rather than
stimulating the receptor as in Graves' disease) has also been proposed.
Diagnosis of hypothyroidism:
The diagnosis of Hashimoto's disease is usually easy:
 Based on the presence of goiter.
 Circulating thyroid autoantibodies
 Low circulating concentrations of thyroid hormones with high TSH concentrations.
Clinical features of hypothyroidism:
Symptoms (Common)
• Fatigue (~ 90%)
• Cold intolerance (80%)
• Depression (~ 70%)
• Poor concentration (~ 65%)
• Musculoskeletal aches and pains(~ 25%)
• Carpal tunnel syndrome(~ 15%)
Less common
• Constipation (~ 50%)
• Hoarse voice (~ 40%)
• Menorrhagia (~ 30%)
Signs (Common )
• Dry, scaly skin (~ 90%)
• Coarse, brittle thinning hair (~60%)
• Bradycardia (~ 40%)
• Hair loss or dryness (~ 70%)
• Anemia
• Puffy eyes (~ 90%)
Less common
• Edema (~ 30%)
• Cerebellarataxia*
• Deafness*
• Psychiatric*

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Treatment of primary hypothyroidism:
 Use of the prohormone thyroxine in the treatment of primary hypothyroidism is cheap
and easy to monitor.
 The conversion of T4 to T3 is physiologically regulated and the dose can be altered
according to serum TSH concentrations.
 No attempt is made to treat the underlying immune disorder.
 Severe hypothyroidism resulting in 'myxedema coma' is not often seen nowadays but
may require parenteral T4 or T3 in addition to general supportive measures and
hydrocortisone.
 It is to be noted that some physiological conditions such as pregnancy may increase T4
requirements.
 Whilst gastrointestinal diseases or drugs such as sucralfate may decrease its absorption.
Requirements may also be increased by drugs increasing its clearance such as
rifampicin whilst some such as amiodarone may decrease T4 to T3 conversion.
 Diseases such as cirrhosis of the liver or the natural processes of ageing may decrease
requirements.
The terms 'compensated hypothyroidism' or 'decreased thyroid reserve'
have been used to indicate the situation in which:
 Circulating T4 or T3 concentrations are low-normal but
 Serum TSH concentrations are elevated.
There has been discussion over when such patients should be treated with T4.
In this controversial area, some have argued that patients with serological evidence of anti-
thyroid antibodies are likely to develop clinical hypothyroidism and should be treated.
Myxedematous Coma:
 It is a life threatening, end-stage expression of hypothyroidism.
 Characterized by :
 Coma, hypothermia, cardiovascular collapse, hypoventilation,
 Severe metabolic disorders that include hyponatremia, hypoglycemia, and lactic
acidosis.
 It occurs most often in elderly women who have chronic hypothyroidism from a
spectrum of causes.
 It occurs more frequently in the winter months, which suggests that cold exposure may be
a precipitation factor.
 The severely hypothyroid person is unable to metabolize sedatives, analgesics, anesthetic
drugs, and buildup of these agents may precipitate coma.
 Treatment includes aggressive management of precipitating factors; and thyroid
replacement therapy.

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Subclinical hypothyroidism:
Either no symptoms or minimal symptoms suggestive of hypothyroidism with normal serum
free T4 and T3 and elevated serum TSH concentrations.
 Subclinical hypothyroidism is especially common in elderly women, particularly in those
with underlying Hashimoto's thyroiditis, reaching up to 15% in some series.
 Thyroid peroxidase antibodies should be measured in all patients with subclinical
hypothyroidism.
 L-Thyroxine therapy is recommended in those patients with positive antibodies because
they are at greatest risk to progress to overt hypothyroidism.
 In the absence of positive antibodies, L-thyroxine therapy is more debatable but might be
advisable in the presence of even suggestive symptoms of hypothyroidism.
 At the least, thyroid function should be closely monitored to determine whether more
severe hypothyroidism develops.

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 Hypothyroidism in the newborn (Congenital)

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Causes
• A missing or abnormally developed thyroid gland
• Pituitary gland's failure to stimulate the thyroid
• Defective or abnormal formation of thyroid hormones
Symptoms
 Most affected infants have few or no symptoms, because they only have a mild decrease
in thyroid hormone production.
 However, infants with severe hypothyroidism often have a distinctive appearance.
Symptoms may include:
 Puffy-appearing face
 Dull look
 Thick, protruding tongue
Two cases of hypothyroidism

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Two cases of hypothyroidism, patient before (A and C) and after (B and D) after full
replacement with thyroid hormone recovered from hypothyroidism.
In fig A, Notice the loss of eyelashes, the areas of vitiligo around the mouth, the region around
the eyes, and the scalp. In figure-C, Notice the lethargic expression and the periorbital puffiness
disappears with therapy (D).
Hyperthyroidism
Hyperthyroidism, or Thyrotoxicosis: is
 The reaction to Excess production of thyroid hormone & Excessive delivery of thyroid
hormone to the peripheral tissues.
Types of hyperthyroidism include:
1) Graves’ disease (GD) - the most common form - an autoimmune disease.
2) Toxic multinodular goiter - occurs later in life. Nodules are insidious and almost never
malignant. No ophthalmopathy or localized myxedema present.
3) Toxic uninodular goiter - solitary nodule with autonomous function.Almost always
benign.
4) Thyroid crisis, or Storm, is an acutely exaggerated manifestation of the hyperthyroid
state.
Predominant age: Any age, peaks in 3rd and 4th decades
Predominant sex: Female > Male (5:1 ratio)
Causes:
 Graves' disease - autoimmune disease
 Toxic multinodular goiter - iodine deprivation followed by iodine repletion
 Toxic uninodular goiter - unknown
Other causes are rare and include:
 TSH-secreting pituitary tumors.
 Ingestion of excessive thyroid hormone (T4 or T3).
 Iodine-induced hyperthyroidism, especially from the cardiac drug amiodarone
 Functioning trophoblastic tumors.
o Is a group of rare tumors that form in the tissue that surrounds an egg after it is fertilized.
o This tissue is made of trophoblast cells, which connect the fertilized egg to the
wall of the uterus and form part of the placenta.
o A tumor forms instead of a healthy fetus.

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Diagnosis:
 Thyroid hormone functions as a controller of the metabolic rate of all of the processes
in the body.
 In Hyperthyroidism every function of the body tends to speed up.
 Therefore, some of the symptoms of hyperthyroidism are
 nervousness,
 irritability,
 heart racing,
 hand tremors,
 anxiety,
 difficulty sleeping,
 thinning of the skin,
 fine brittle hair, and
 muscular weakness—especially in the upper arms and thighs.
 More frequent bowel movements may occur, but diarrhea is uncommon.
 Weight loss, sometimes significant, despite a good appetite may occur, vomiting,
 In women, menstrual flow may lighten and menstrual periods may occur less often.
The criteria for establishing the diagnosis are:
 Subtle (‫ﻣﻠﺤﻮﻅﺔ‬ ‫)ﻏﻴﺮ‬symptoms and signs of hyperthyroidism,
 A normal free T4 level, and
 A suppressed serum TSH level.
 Measurement of the TSH receptor antibodies is rarely necessary except during the last
trimester of pregnancy to predict the possible occurrence of neonatal Graves' disease;
TSH receptor antibodies readily cross the placenta to stimulate the fetal thyroid.
 Most patients with Graves' disease have circulating anti thyroid peroxidase antibodies
(anti TPO) and fewer have anti thyroglobulin antibodies. Since measurements of these
antibodies are readily available in most laboratories, they may aid in determining if the
hyperthyroidism has an autoimmune cause.
 T3 toxicosis is difficult to diagnose because T3 usually is not measured when evaluating
thyroid function unless the patient has a suppressed serum TSH and normal free T4
levels.
Treatment of hyperthyroidism:
Is directed toward reducing the level of thyroid hormone: by
 Eradication of the thyroid gland with radioactive iodine (Destruction of thyroid tissue
with radioactive iodine is used more frequently than surgery.)
 Through surgical removal of part or all of the gland
 Use of drugs that decrease thyroid function and thereby the effect of thyroid hormone
on the peripheral tissues.

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 The B-adrenergic-blocking drug propranolol may be used to block the effects of the
hyperthyroid state on sympathetic nervous system function.
 It is given in conjunction with other antithyroid drugs such as propylthiouracil and
methimazole.
 These drugs prevent the thyroid gland from converting iodine to its
organic( hormonal ) form
 Block the conversion of T4 to T3 in the tissues.
Graves’ disease
 Graves’ disease is a state of :
 Hyperthyroidism,
 Goiter, and
 Ophthalmopathy ( exophthalmos, i.e., bulging of the eyeballs)
 The onset usually is between the ages of 20 and 40 years,
 Women are five times more likely to experience the disease than men.
 Graves’ disease is an autoimmune disorder characterized by abnormal stimulation of the
thyroid gland by thyroid–stimulating antibodies (thyroid-stimulating
immunoglobulins (TSI's) of the IgG class are produced and bind to thyrotropin (TSH)
receptors on the thyroid gland. (Thyrotropin is also called TSH )
 The TSI's mimic the action of TSH and cause: Excess secretion of thyroxine (T4) &
triiodothyronine (T3).
 It may be associated with other autoimmune disorders such as myasthenia gravis and
pernicious anemia.
o Myasthenia gravis "grave muscle weakness" is a rare chronic autoimmune
neuromuscular disease characterized by weakness of the skeletal (voluntary)
muscles of the body without atrophy, and caused by a defect in the action of
acetylcholine at neuromuscular junctions.
 The disease is associated with human leukocyte antigen (HLA)-DR3 and HLA B8, and a
familial tendency is evident.

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 The Exophthalmos, which occurs in as many as one third of persons with Graves’
diseases, is thought to result from thyroid stimulating antibodies sensitized to interact with
antigens found in fibroblasts in orbital tissue behind the eyeball and in the extramural
muscles that move the eyeball.
 The ophthalmopathy of Graves’ disease can cause severe eye problems:
 paralysis of the extra ocular muscles;
 involvement of the optic nerve, with some visual loss,
 corneal ulceration because the lids do not close over the protruding eyeball.
 The exophthalmoses usually tend to stabilize after treatment of the hyperthyroidism.
 Unfortunately, not all of the ocular changes are reversible with treatment.
 Smoking tends to aggravate the condition.
Goiter
Exophthalmos
Subclinical Hyperthyroidism
No symptoms or minimal symptoms of hyperthyroidism with normal serum free T4 and T3
concentrations and low serum TSH concentrations.
 Subclinical hyperthyroidism is far less common than subclinical hypothyroidism , but
has been associated with an increased incidence of atrial fibrillation in the elderly.
Whether antithyroid drug therapy is indicated under these conditions is unclear and
further studies are necessary.
 Prospective thyroid function tests should be closely monitored and therapy instituted if
even a minimal elevation in serum free T4 or T3 values or atrial fibrillation occurs.

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Thyroid storm
Thyroid storm, or crisis, is an extreme and life-threatening form of thyrotoxicosis. rarely seen
today because of improved diagnosis and treatment methods.
When it does occur, it is seen most often in undiagnosed cases or in persons with hyperthyroidism
who have not been adequately treated.
It often is precipitated by Stress such as:
 an infection (usually respiratory),
 diabetic ketoacidosis,
 physical or emotional trauma,
 manipulation of a hyperactive thyroid gland during thyroidectomy.
Thyroid storm is manifested by:
 a very high fever,
 extreme cardiovascular effects (e.e., tachycardia, congestive failure, and angina),

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 severe CNS effects (i.e. agitation, restlessness, and delirium).
Thyroid storm requires rapid diagnosis and implementation of treatment.
Summary:
Thyroid hormones play a role in the metabolic process of almost all body cells and are necessary
for normal physical and mental growth in the infant and young child.
 Hypothyroidism can occur as a congenital or an acquired defect.
 Congenital hypothyroidism leads to mental retardation and impaired physical growth
unless treatment is initiated during the first months of life.
 Acquired hypothyroidism leads to a decrease in metabolic rate and an accumulation
of a mucopolysaccharide substance in the intercellular space; this substance attracts
water and caused a mucous type of edema called Myxedema.
 Hyperthyroidism causes an increase in metabolic rate and alterations in body function
similar to those produced by enhanced sympathetic nervous system activity.
 Graves’ disease, which is caused by thyroid-stimulating antibodies, is characterized
by hyperthyroidism, goiter and ophthalmopathy.

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PARATHYROID HORMONE
 Parathyroid hormone is secreted from 4 glands located on the dorsal surface of the
thyroid gland.
 The glands weigh an average of 40 mg each.
 PTH is an 84-amino acid polypeptide secreted by the parathyroid glands.
 It has several actions, but perhaps the most important is to defend against
Hypocalcemia.
 Although the thyroid and parathyroid glands are neighbors and both are part of the
endocrine system, they are otherwise unrelated.
 Calcitonin (also known as thyrocalcitonin) is a 32-amino acid polypeptide hormone that
is produced by the parafollicular cells (C-cells) of the thyroid. It acts to reduce blood
calcium (Ca2+), opposing the effects of parathyroid hormone (PTH).
 The main function of PTH is to maintain the calcium concentration of the extra cellular
fluids :
1) by promoting the release of calcium from bone.
2) PTH enhances distal tubular Ca reabsorption.
3) PTH also decreases renal PO4 reabsorption and thus increases renal PO4 losses.
 Renal PO4 loss prevents the solubility of calcium phosphate from being exceeded
in plasma as Ca levels rise in response to PTH.
4) PTH also influences vitamin D metabolism ;
 Vitamin D is converted to its most Active Form ;1,25-dihydroxycholecalciferol
[1,25(OH)2D3], in the kidney by the enzyme 1—hydroxylase . 1,25(OH)2D3.
PTH enhances intestinal Ca absorption through increased formation of 1,25(OH)2D3 which
increases the percentage of dietary Ca that is absorbed by the intestine).
5) Despite this effect on Ca absorption from the GI tract, long-term increases in PTH
secretion generally result in further bone resorption by inhibiting osteoblastic function and
promoting osteoclastic activity.

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Regulation of Calcium
Parathyroid glands produce parathyroid hormone, which acts to raise blood calcium levels by
both absorbing more calcium from kidneys and gut, and by causing bones to break down and
release some of their calcium stores
 Parathyroid cells sense:
 decreases in plasma Ca, presumably through a Ca receptor,
 increase PTH gene expression and
 Release preformed PTH into the circulation.
 Magnesium serves as a cofactor in the generation of cellular energy and is important in
the function of second messenger systems.
 Magnesium affects the synthesis and release of PTH. Because of its function in
regulating PTH release, severe and prolonged hypomagnesaemia can markedly inhibit
PTH levels.

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Regulation of serum calcium concentration by parathyroid hormone
Assay of PTH
 Elevated serum PTH concentration (the normal range for PTH is 10–60 pg/mL (1–6
pmol/L)
 Hypercalcemia
o If hypercalcemia results from some form of hyperparathyroidism, then the
serum PTH level will be high;
o If hypercalcemia has a nonparathyroid basis, then PTH will be suppressed.
 10-20% of patients with primary hyperparathyroidism have normal serum calcium
concentrations. These patients typically come to medical attention in the setting of an
evaluation for low bone mineral density. In some patients this may be due to concomitant
vitamin D deficiency.

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 Other lab. findings:
o low serum phosphorus,
o increased urinary calcium excretion,
o elevated serum 1,25-dihydroxyvitamin D,
o decreased tubular reabsorption of phosphorus
o elevated urinary excretion of nephrogenous cAMP (Cyclic Adenosine
Monophosphate)
VITAMIN D
The term vitamin D (calciferol) refers to 2 secosteroids:
 Vitamin D2 (ergocalciferol) and
 Vitamin D3 (cholecalciferol).
Since vitamin D can be formed in vivo (in the epidermis) in the presence of adequate amounts
of ultraviolet light, it is more properly considered a hormone (or prohormone) than a vitamin.
Vitamin D3 is formed in the skin from 7-dehydrocholesterol, which is distributed throughout the
epidermis and dermis but has its highest concentration in the lower layers of the epidermis.
These epidermal layers also account for the highest production of vitamin D.
Hypoparathyroidism
Hypoparathyroidism reflects deficient PTH secretion resulting in hypocalcemia. May be due:
1. Congenital absence of all of the parathyroid glands, such as occurs in Digeorge
syndrome.
2. An acquired deficiency of PTH may occur after neck surgery, particularly if the
surgery involves removal of a parathyroid adenoma, thyroidectomy, or bilateral neck
resection for cancer.
3. An autoimmune origin. Antiparathyroid antibodies particularly those with
multiple endocrine disorders.
4. Heavy metal damage, such as occurs with Wilson’s disease, metastatic tumors, and
infection.
5. Magnesium deficiency: causes functional impairment of parathyroid function.
Correction of the hypomagnesemia results in rapid disappearance of the condition.
Symptoms of acute hypoparathyroidism:
 Result from a decrease in serum calcium include:
 Tetany with muscle cramps, carpopedal spasm, and convulsions.
 Paresthesias, such as tingling of the circumoral area and in the hands and feet.
 There may be prolongation of the QT interval caused by low calcium levels,
resistance to digitalis, hypotension, and refractory heart failure.

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Symptoms of chronic hypoparathyroidism:
 Lethargy, anxiety state, and personality changes.
 Blurring of vision caused by cataracts. (Which develop by time).
 Extrapyramidal signs, such as those seen with Parkinson’s disease, may occur
because of calcification of the basal ganglia.
 Successful treatment of the Hypocalcemia may improve the disorder and is sometimes
associated with decreases in basal ganglia calcification on x-ray . Teeth may be
defective if the disorder occurs during childhood.
Diagnosis of hypoparathyroidism:
 serum calcium levels,
 serum phosphate levels
 serum PTH levels.
Serum magnesium levels are usually measured to exclude hypomagnesemia as a cause of the
disorder.

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 Trousseau’s sign: In this test the sphygmomanometer cuff is inflated to 300
mmHg for 3 minutes. The carpopedal spasm is painful.
 Chvostek’s sign: Tapping the facial nerve anterior to ear causes facial muscle
twitching
Treatment:
Acute hypoparathyroidism tetany :
 Treated with intravenous calcium gluconate
 followed by oral administration of calcium salts and vitamin D.
 Magnesium supplementation is used when the disorder is caused by magnesium
deficiency.
chronic hypoparathyroidism:
 Treated with oral calcium and vitamin D.
 Serum calcium levels are monitored at regular intervals |(at least every 3 months) as means
of maintaining serum calcium within this range helps to prevent hypercalciuria and kidney
damage.

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Common Effects of Parathyroid Hormone Imbalance
Pseudohypoparathyroidism
 Is a rare familial disorder.
 Two distinct forms of pseudohypoparathyroidism are recognized.
 Pseudohypoparathyroidism type 1B is a disorder of
o isolated resistance to PTH,
o Hypocalcemia,
o Hyperphosphatemia and
o Secondary Hyperparathyroidism.

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 Pseudohypoparathyroidism type 1A has,
o in addition to the above biochemical features (↓ Ca ,↑P, ↑PTH )
o a characteristic somatic phenotype known as Albright's hereditary osteodystrophy.
This consists of short stature, a round face, short neck, brachydactyly (short digits),
and subcutaneous ossifications
 The manifestations of the disorder are primarily attributable to hypocalcemia.
 Treatment if similar to that for Hypoparathyroidism.
Hyperparathyroidism
Hyperparathyroidism is caused by hyper secretion of parathyroid hormone.
 Primary Hyperparathyroidism:
Caused by:
 Hyperplasia }
 adenoma, or } of the parathyroid glands
 carcinoma }
 more commonly after age 50 years and is
 more common in women than men.
 causes hypercalcemia and an increase in calcium in the urine filtrate, resulting in
hypercalcuria and the potential for development of kidney stones.
 Chronic bone resorption may produce diffuse demineralization, pathologic fractures, and
cystic bone lesions.
 Diagnosis :
 ↑ Serum calcium and PTH levels.
 Imagine studies of the parathyroid area may be used to identify a parathyroid
adenoma.
 Signs and Symptoms
The signs and symptoms of primary hyperparathyroidism are those of hypercalcemia. They are
classically summarized by the mnemonic:
"stones, bones, abdominal groans and psychiatric moans".
 "Stones" refers to kidney stones, nephrocalcinosis, and diabetes insipidus (polyuria and
polydipsia). These can ultimately lead to renal failure.
 "Bones" refers to bone-related complications. The classic bone disease in
hyperparathyroidism is osteitis fibrosa cystica, which results in pain and sometimes
pathological fractures. Other bone diseases associated with hyperparathyroidism
are osteoporosis, osteomalacia, and arthritis.
 "Abdominal groans" refers to gastrointestinal symptoms of constipation, indigestion,
nausea and vomiting. Hypercalcemia can lead to peptic ulcers and acute pancreatitis.
 "Psychiatric moans" refers to effects on the central nervous system. Symptoms include
lethargy, fatigue, depression, memory loss, psychosis, ataxia, delirium, and coma.
 Left ventricular hypertrophy
 Proximal muscle weakness, itching

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 Secondary hyperparathyroidism
 occurs primarily in persons with Renal Failure
 involves hyperplasia of parathyroid glands.

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Pathophysiology:
 In early renal failure:
o An  PTH results from: serum calcium and activated vitamin D levels.
o As renal failure progresses: in vitamin D and calcium receptors
 making the parathyroid glands more resistant to vitamin D and calcium.
 At this point,  phosphate levels hyperplasia of the parathyroid glands independent of
calcium and activated vitamin D.
 The bone disease seen in persons with secondary hyperparathyroidism caused by renal
failure is known as renal osteodystrophy.
Treatment of Hyperparathyroidism:
1. Resolving the hypercalcemia with large fluid intake.
2. Persons with mild disease :
a) advised to keep active and drink adequate fluids.
b) to avoid calcium-containing antacids, vitamin D, and thiazide diuretics,
which reabsorption of calcium by the kidney.
3. Bisphosphonates (e.g., pamidronate and alendronate), which are potent inhibitors of
bone resorption, may be used temporarily to treat the hypercalcemia of
hyperparathyroidism.
4. Parathyroidectomy may be indicated in persons with :
symptomatic hyperparathyroidism,
kidney stones , or
bone disease.