parathyroid hormone pathophysiology

1. PATHOPHYSIOLOGY OF
PARATHYROID
HORMONE
DR. PATRICK GICHERU
SUPERVISOR: DR. T. K. MWENDWA

2. OBJECTIVES
• Normal physiology recap
• hyperparathyroidism
• Hypoparathyroidism
• PTHrP

3. Calcium homeostasis
• Maintenance of calcium and phosphate homeostasis is
under the influence of two polypeptide hormones;
• parathyroid hormone(PTH)
• calcitonin (CT),
• as well as a sterol hormone, 1,25 dihydroxy cholecalciferol
(1,25 (OH)2D3. (calcitriol)

4. Calcium and phosphate metabolism

5. Control of PTH secretion
• Under influence of serum Ca2+
• Increased levels = -ve FB via
CaSR
• Low levels = low CaSR activity
• Calcitriol: negative feedback, via
vit D receptor prevents gene
expression
• normal levels 10-55 pg/ml

6. Pathophysiology of parathyroid hormone
• The pathophysiology of the PTH system will include the following:-
1.excess of PTH;
2.a deficiency of PTH;
3. target tissue resistance to PTH.

7. Hyperparathyroidism
• abnormal hypersecretion of parathyroid hormone (PTH),
producing hypercalcemia and hypophosphatemia
• May be:
• primary
• Secondary
• tertiary

8. Primary hyperparathyroidism
• over secretion of PTH by one or more parathyroid glands.
• Usually due to combination of
• decreased sensitivity to calcium, (decreased functional CaSRs)
• or an increase in parathyroid cell mass, or both.
• Demographics
• 5-50 per 10,000 individuals.
• common after 40 years
• female-to-male ratio of 3:1.

9. 1° hyperPTH cont.
causes
• Glandular adenomas – 89%. Usually solitary. Multiple <2%
• Gland hyperplasia – about 6%. Usually all 4
• Carcinomas – rare.
• Familial syndromes – part of MEN 1 and MEN 2a syndromes

10. 1° hyperPTH cont.
clinical consequences
• Presents with features of
hyperCa2+
• Skeletal syndrome
• Renal syndrome
• Gastrointestinal syndrome
• other

11. 1° hyperPTH cont.
skeletal presentation
• Osteitis fibrosa cystica
• Due to osteoclastic activity – bone
demineralization
• Presentation with bone pain
• Subperiosteal bone resorption ,
brown tumours on xray

12. 1° hyperPTH cont.
renal presentation
• Nephrolithiasis – upto 80% of cases
• hypercalciuria,
• nephrocalcinosis,
• chronic renal insufficiency,
• renal tubular dysfunction

13. 1° hyperPTH cont.
other presentation
• Neuromuscular: Muscle weakness, fatigue/malaise
• Neurologic: Depression, nervousness, cognitive dysfunction,
psychosis, confusion, headache
• Gastrointestinal: Peptic disease, pancreatitis, cholelithiasis, nausea,
vomiting, loss of appetite, constipation, abdominal pain
• Cardiovascular:, arrhythmias
• MX: usually surgical

14. Secondary hyperparathyroidsm
• compensatory hyperfunctioning of the parathyroid glands
• caused by hypocalcemia or peripheral resistance to
parathyroid hormone (pseudohypoparathyroidsm)
• Hyperplasia of parathyroid glands
• Commonly due to renal failure, esp with poor nutrition and
advanced age
• Other causes:
• calcium malabsorption,
• vitamin D deficiency, or deranged vitamin D metabolism

15. 2° HPT cont.
renal cause

16. 2° HPT cont.
clinical presentation
• Similar to 1° hyperPTH but milder
• Nephrolithiasis and calcinosis less common.
• Renal osteodystrophy with generalized osteopenia and multiple
pathological #’s
• Osteodystrophy causes bone pain, proximal muscle weakness
• MX: addressing underlying issue

17. Tertiary hyperparathyroidism
• Occurs post secondary hyperparathyroidism (HPT) in which the
glandular hyperfunction and hypersecretion continue despite
correction of the underlying abnormality,
• Seen post renal transplant
• development of autonomous (unregulated) function after sustained
stimulation.
• MX; parathyroidectomy

18. PTHrP
• PTH like activity via PTH 1 receptors
• Role in embryology
• Commonest cause of hyper Ca2+
in non mets solid tumours
• AKA humoral hypercalcemia of malignancy (HHM)
• Upto 80% of all hyper Ca2+
in Ca
• Commonly breast, lung, renal, ovarian SCC

20. Hypoparathyroidism
• Parathyroid gland hypofunction.
• Hallmark: low PTH, serum Ca2+
with high Po4-
• Prevelence after 45yrs
• M:F - 1:3
• Affects 22 per 100,000 people
• 1° hypoPT – related to gland pathology
• 2° hypoPT – a physiologic state secondary hypercalcemia.

21. Hypoparathyroidism cont.
causes
• Due to; gland destruction;
• Surgical
• Autoimmune
• irradiation
• storage or infiltrative diseases
• Abnormal development; DiGeorges syndrome
• Gene mutations
• Functional causes – neonatal hypoPT, hypomagnesemia.

22. Hypoparathyroidism cont.
causes: gene mutation
• CaSR gene – sensitive set point
• signal peptide sequence of
preproPTH

23. Hypoparathyroidism cont.
clinical consequences
• Due to low Ca2+
• May be variably symptomatic.
• Mainly neuromuscular irritability.

24. Hypoparathyroidism cont.
clinical consequences

25. Hypoparathyroidism cont.
Labs
• PTH
• Ca2+
• Mg2+
• Po4-
• D3

26. Hypoparathyroidism cont.
Mx
• Control of calcium levels
• Calcium suppliments and vitamin D.
• Recombinant human parathyroid hormone (rhPTH[1-84], Natpara)
-adjunct to calcium and vitamin D

27. quiz
A B C D

28. quiz
• A 52-year-old female presents with nausea, fatigue, muscle
weakness,
and intermittent pain in her left flank.
• Laboratory examination reveals an increased serum calcium and a
decreased serum phosphorus.
• The patient’s plasma parathyroid hormone levels are increased, but
parathyroid hormone related peptide levels are within normal limits.
Urinary calcium is increased, and microhematuria is present. The
patient’s
abnormality is most likely caused by
a. Primary hyperparathyroidism
b. Primary hypoparathyroidism
c. Pseudohypoparathyroidism
d. Secondary hyperparathyroidism
e. Secondary hypoparathyroidism