The hypo-hyper syndrome.

he coexistence of thyroid and parathyroid diseases is not rare. In the review of the recent literature, 25% of the patients with primary hyperparathyroidism (PHPT) had significant associated thyroid diseases including carcinoma in an Australian series.1 Regal et al,2 reported a high prevalence of unsuspected varieties of thyroid disease occurring mainly in postmenopausal women in patients with PHPT in another series from Spain.2 Reciprocally, parathyroid pathology has been described in patients with primary thyroid disease. Sinaesi et al,3 carried out the results of a recent Italian series of 221 thyroidectomies showed that 29 patients (13%) had a preoperative subclinical PHPT out of which 19 turned out to be due to parathyroid adenoma or hyperplasia.3 In this communication, we described a rare association of hypothyroidism as part of a polyglandular autoimmune syndrome (PAS) in a patient who in addition, found to have asymptomatic PHPT. A 56-year-old Omani female and a mother of 10 children was attending the medical clinic for last few years for hypertension and hyperlipidemia. She was noticed to have developed several patches of vitiligo and had also complained of alopecia. She required a combination of atenolol, amlodipine, prazosin, indapamide, and losartan to control her hypertension. The patient had a hysterectomy in 1997, and a laparoscopic cholecystectomy in 2002. At a later point, she began to complain of bilateral pain and tingling in both hands, which turned out to be due to the carpal tunnel syndrome (CTS). Positive nerve conduction studies confirmed the diagnosis. That finding prompted further investigations for a possible underlying thyroid disease. Her serum free thyroxine (FT4) was low (6.07 pmol/l; normal = 9-19) with a high level of thyroid-stimulating hormone (TSH) (7.02 uIU/ml, normal = 0.35-4.94) and markedly elevated thyroid antibodies (antithyroglobulin levels of 546 U/ml, normal = 0-15 and anti-peroxidase antibodies levels of 350 U/l, normal = 0-32) were consistent with hypothyroidism due to autoimmune thyroid disease. Other investigations including the hemogram, blood chemistry, other endocrine workup, electrocardiogram, and relevant radiography were initially within normal limits or values. Serum B12 and folate were also within normal ranges. According to Betterle et al4 classification, the diagnosis of PAS type 3 on the basis of hypothyroidism secondary to autoimmune T thyroiditis, vitiligo, and alopecia areata. There was no family history of similar illness. Antibodies for liver kidney microsomal, adrenal gland, gastric parietal cell, intrinsic factor, and acetylcholine receptor antibodies were negative. Facilities for tyrosinase and tyrosine hydroxylase antibodies were not available to our laboratory. The human leukocyte antigen typing revealed A2, A26, B8, B18, DR (17) 3, DR 52, and DQ 2. This haplotype is different from those commonly associated with type 1 PAS (A3 and A28) or type 2 (DR3/DQB1 or DR4/DQB1).4 We gradually commenced the Lthyroxine in increasing doses with noticeable improvement of the CTS symptoms on subsequent visits. We also achieved good suppression of TSH and normalization of serum thyroxine. In further follow-up, we discovered that she has asymptomatic hypercalcemia due to PHPT following repeated routine assays of serum calcium and phosphorous. The calcium reached 12.7 and 12.9 mg/dl (normal = 8.5-10.5) along with marginally reduced level of phosphorous of 2.2 mg/ dl (normal = 2.5-4 mg/dl) and repeatedly, markedly raised serum parathyroid hormone of 293 and 312 pg/ml (normal = 11-62 pg/ml). The urinary calcium excretion was 285 mg/day (normal = 100-300 mg/ day). The radioisotope scan of the parathyroid glands (Tc 99m-sestamibi), and neck ultrasound examination both confirmed the presence of right inferior parathyroid adenoma. The clinical setting of hyperparathyroid adenoma in a hypertensive patient warranted further work-up to exclude multiple endocrine neoplasia (MEN) syndrome type I or type II A. Assays for serum prolactin, follicle stimulating hormone, luteinizing hormone, insulin, growth hormone, insulin-like growth factor, cortisol, adrenocorticotropic hormone, calcitonin, and 24 hours urine for vanillylmandelic acid (VMA) were within normal values. Serum gastrin was moderately elevated at 67 pmol (normal = 0-43); but not sufficiently high to diagnose pancreatic gastrinoma. Nonetheless, the Indium 111-Octreotide scan was negative for neuroendocrine tumor in pancreas or elsewhere in the abdominal cavity. The findings of the pituitary CT were negative for pituitary tumor and the iodine-131 metaiodobenzylguanidine (MIBG) scans were negative for pheochromocytoma. Subsequently, she underwent successful excision of the parathyroid adenoma resulting in normalization of her serum calcium and phosphorous. The histopathology confirmed a well capsulated parathyroid adenoma with a wedge thyroid tissue showing focal lymphocytic thyroiditis. Polyglandular autoimmune syndrome 3 has been classified into 3 subcategories A, B and C. The latter is characterized by autoimmune thyroiditis with vitiligo and alopecia, or both and other organ The hypo-hyper syndrome