Pseudohypoparathyroidism Type 1B with Hypothyroidism

Case Report

Indian Pediatr 2012;49: 667-668

	Pseudohypoparathyroidism Type 1B with Hypothyroidism
Rajesh Joshi and Muznah Kapdi From the Department of Pediatrics, BJ Wadia Hospital for Children, Parel, Mumbai. Correspondence to: Dr RR Joshi, Department of Pediatrics, BJ Wadia Hospital for children, Parel, Mumbai. Email: [email protected] Received: December 13, 2011; Initial review: January 09, 2012; Accepted: February 13, 2012
Pseudohypoparathyroidism due to deficient end organ response to parathyroid hormone (PTH) is characterized by hypocalcemia, hyperphosphatemia and increased serum PTH. We report a case of an 8-year-old girl with pseudohypoparathyroidism without features of Albright’s hereditary osteodystrophy. The case is of interest as the child on serial follow-up over a period of 2 years developed hypothyroidism. This is a rare feature seen in pseudohypoparathyroidism type1b. Key words: Albright’s hereditary osteodystrophy, Hypothyroidism, Parathyroid hormone, Pseudohypoparathyroidism.
Pseudohypoparathyroidism (PHP) is a group of disorders characterized by resistance to parathyroid hormone, resulting in hypocalcemia. Several types of PHP have been identified: Type 1a- presents with features of Albright hereditary osteodystrophy (AHO - short stature, obesity, round facies, subcutaneous ossifications, brachydactyly and mental retardation in some patients) and types 1b and 2 (without features of AHO) [1] . We report a patient with PHP without features of AHO who developed hypothyroidism on follow up. Case Report An 8-years-old girl presented with involuntary inward turning of thumb and tingling in hands for 3 months.She had similar complaints one year back, which were diagnosed as hypocalcemia (serum calcium-7.9 mg/dL). She was treated with calcium supplements for 2 months following which she had temporary relief. She weighed 25 kg and measured 125 cm in height (within normal centiles). Examination did not reveal skeletal abnormalities or dysmorphism. Chvostek’s and Trousseau’s sign were positive. Laboratory investigation revealed serum calcium 6.6 mg/dL, iCa⁺⁺–0.83 mmol/dL (low), serum phosphorous 7.4 mg/dL(high) and alkaline phosphatase 187 IU/mL (normal levels). Levels of parathyroid hormone were very high (iPTH-560pg/mL; normal value: 8.9-59.8 pg/mL). Complete blood count, 25OH-vitamin D, and liver and renal function tests were normal. Thyroid functions (TFT) were normal [free(f)T³–3.2 pg/mL; fT⁴–1.3 ng/dL; TSH-5 IU/mL]. She was treated with calcium supplements and calcitriol. On follow up, serum calcium levels and urinary calcium/creatinine were monitored to achieve good calcemic control and to prevent calciuria . TFT were monitored six monthly. She developed hypothyroidism (TSH: 15.5 IU/mL; fT³: 3.68 pg/mL; fT⁴:1.19 ng/dL) two years after diagnosis, for which she was treated with thyroxine 50 mcg daily and subsequently increased to 75 mcg. She is now 11½-year old, having normal growth and pubertal changes (thelarche). The underlying pathophysiology in PHP is a defect at the PTH-receptor (genetic mutation in the alpha subunit of the receptor G-protein causing altered messenger action), leading to end organ resistance to the action of PTH. Resistance to other hormones (which function via the alpha subunit of G protein), most commonly thyroid-stimulating hormone and rarely gonadotrophins and growth hormone releasing hormone may be seen in type 1a [2,3]. PHP Ib typically shows no other endocrine abnormalities, although resistance to thyroid-stimulating hormone (leading to primary hypothyroidism) has been reported rarely [4,5] PHP type 2 does not present with any other hormone resistance . Our patient probably had PHP type1b. PHP Ib is caused by deletions in the differentially methylated region (DMR) of the GNAS locus, located on chromosome 20q13.11. It is mostly a sporadic disorder, but sex-influenced autosomal dominant inheritance has been reported [1]. Parents of our patient did not have any phenotypic or biochemical evidence of PHP. PHP type Ib is characterized by renal PTH resistance whereas PTH responsiveness is preserved in the bone and other tissues resulting in lack of AHO features.Measurement of cAMP excretion after PTH infusion is a differentiating feature between type 1b and 2 (decreased in type 1b and normal in type 2) [2]. However, this test was not affordable. Administration of oral calcium and calcitriol remains the mainstay of treatment. The goals of therapy are to maintain serum calcium levels within the reference range so as to avoid hypercalciuria. Thyroid function tests should be evaluated periodically even in absence of features of AHO, as hypothyroidism develops rarely, as seen in our patient. Acknowledgement: We are grateful to Dr Y K Amdekar , Medical Director B J Wadia hospital for children for allowing us to publish this case report. Contributors: RJ diagnosed and treated the patient. MK was involved in treatment of the patient. Both of them wrote the article. Funding: None; Competing interests: None stated. References 1. Mantovani G, Spada A. Mutations in the Gs alpha gene causing hormone resistance. Best Prac Res Clin Endocr Metab. 2006;20:501-13. 2. "Online Mendelian Inheritance in Man (OMIM), a knowledgebase of human genes and genetic disorders". Nucleic Acids Research 33 (Database issue): D514–D517. Available from: http://en.wikipedia.org/wiki/OMIM. Accessed July 19, 2011 3. Mariot V, Maupetit-Mehouas S, Sinding C, Kottler ML, Linglart A. A maternal epimutation of GNAS leads to Albright osteodystrophy and parathyroid hormone resistance. J Clin Endocr Metab. 2008;93:661-5. 4. Levine MA, Downs RW Jr , Moses AM, Breslau NA, Marx SJ, Lasker RD, et al. Resistance to multiple hormones in patients with pseudohypoparathyroidism. Association with deficient activity of guanine nucleotide regulatory protein. Am J Med. 1983;74:545-56. 5. Heinsimer JA, Davies AO, Downs RW, Levine MA, Spiegel AM, Drezner MK, et al. Impaired formation of beta-adrenergic receptor-nucleotide regulatory protein complexes in pseudohypoparathyroidism. J Clin Invest. 1984;73:1335-43.