Hypoparathyroidism without hypocalcaemia — ASN Events
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Hypoparathyroidism without hypocalcaemia (#339)

Teresa Lam 1 , David Chipps 1
  1. Diabetes and Endocrinology, Westmead Hospital, Westmead, NSW

Introduction:

Parathyroid hormone (PTH) deficiency usually results in hypocalcaemia and hyperphosphataemia. Suppression of PTH secretion may occur in non-PTH mediated hypercalcaemia such as with parathyroid hormone-related peptide (PTHrP) mediated hypercalcaemia of malignancy. However, direct suppression of PTH secretion by ectopic PTHrP production in the absence of hypercalcaemia has not been described.    

Case:

A 20 year old immunocompetant woman was admitted in January 2013 with a reduced level of consciousness. In 2012, she had been treated for presumed tuberculosis meningitis.

On admission, she had a normal leukocyte count, creatinine and calcium but an elevated phosphate (1.61 mmol/L). MRI brain revealed hydrocephalus with nodular enhancement, reflecting granulomas. Cerebrospinal fluid showed a raised leukocyte count (125/cm3). Both CSF and serum cryptococcal antigen titres were elevated (128 and 1024 respectively). She was treated for cryptococcal meningitis with induction flucytosine and liposomal amphotericin, then fluconazole consolidation therapy.

Despite clinical improvement, serum phosphate remained elevated, peaking at 1.93 mmol/L (0.81 - 1.45 mmol/L) and serum calcium remained within normal limits. PTH was <0.3 pmol/L (1.0 - 6.8 pmol/L). 25-hydroxyvitamin D was normal, but 1,25 (OH)2D was low at 39 pmol/L (60 – 158 pmol/L). 24-hour urinary phosphate excretion was (inappropriately) normal. Serum PTHrP was elevated at 3.5 pmol/L (0 -1.3 pmol/L).

Discussion:

PTHrP has been shown to mediate hypercalcaemia in granulomatous diseases including sarcoidosis and coccidioidomycosis, suggesting that PTHrP expression may be involved in the normal granulomatous immune response1, 2. PTHrP expression by granulomas is not uniformly associated with hypercalcaemia but when present, PTH secretion is suppressed1. In our patient, PTHrP secretion suppressed PTH secretion, but did not produce hypercalcaemia or prevent hyperphosphataemia, i.e. hypoparathyroidism without hypocalcaemia. This case therefore illustrates the direct inhibitory effects of PTHrP on PTH3, 4, and highlights the differences between PTH and PTHrP on calcium and phosphate balance.

  1. Zeimer HJ, Greenaway TM, Salvin J et al. Parathyroid Hormone-Related Protein in Sarcoidosis. The American Journal of Pathology 1998;152:17-21
  2. Fierer J, Burton DW, Haghighi P, Deftos, L. Hypercalcemia in disseminated coccidiodomycosis: expression of parathyroid hormone-related peptide is characteristic of granulomatous inflammation. Clinical infectious diseases 2012;55(7):e61-6
  3. Horwitz MJ, Tedesco MB, Sereika SM et al. A 7-day continuous infusion of PTH or PTHrP suppresses bone formation and uncouples bone turnover. Journal of bone and mineral research 2011;26(9):2287-97
  4. Plotkin H, Gundberg C, Mitnick M, Stewert AF. Dissociation of bone formation from resorption during 2-week treatment with human parathyroid hormone-related peptide (1-36) in humans: potential as an anabolic therapy for osteoporosis. Journal of Clinical Endocrinology and Metabolism 1998; 83(8);2786-91
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