Hyperthyroidism due to inappropriate TSH secretion with associated hyperprolactinaemia—a case report and review of the literature

Abstract

SummaryA patient with inappropriate thyrotrophin (TSH) secretion is described. She initially presented with classical hyperthyroidism during pregnancy, responded to propylthiouracil and, subsequently, had a normal delivery. Hyperthyroidism persisted and 7 5 months later a subtotal thyroidectomy was performed. After a further 16 months, mild symptoms of hyperthyroidism recurred. She again responded to propylthiouracil, but developed galactorrhoea. At that stage, it was noted that she had persistently elevated circulating TSH in the presence of elevated T4 and T3 levels. Her symptomatology was mild, although objective indices of thyroid activity, including pulse rate, BMR, sex hormone binding globulin and cholesterol, were indicative of hyperthyroidism. CT scan and tomography of the sella were normal.She had a markedly exaggerated TSH response to thyrotrophin releasing hormone (TRH). Basal TSH and responsiveness to TRH was suppressed by high dose dexamethasone. The TSH response to TRH was partially suppressed by exogenous T3, but there was no effect on basal TSH levels. TSH also decreased slightly with L-dopa and bromocriptine. Circulating TSH rose markedly during methimazole administration. TSH a and ,B subunits were elevated and appropriate for the high TSH. In addition, both subunits increased following TRH. The patient had basal hyperprolactinaemia with an impaired prolactin (PRL) response to TRH and metoclopramide. PRL suppressed with L-dopa and bromocriptine. The remaining anterior pituitary function was intact. Most of the laboratory findings argue against the presence of a TSH producing pituitary tumour and the most likely cause for inappropriate TSH secretion in this patient is selective resistance of the thyrotroph to thyroid hormones. A mild element of peripheral resistance might also be present. The hyperprolactinaemia could be related to lactotroph resistance to thyroid hormone.The complexities of treatment in this patient are stressed. Therapy was initially attempted with low dose dexamethasone, but this had no effect. T3 treatment produced an exacerbation of her symptomatology and did not influence basal TSH, thyroid hormones, or 131J uptake. Bromocriptine administration for 11 months partially suppressed basal TSH without influencing T3 and there was an increase in T4. Methimazole did decrease her T4 and T3, but TSH and PRL rose to even greater levels. Her hyperthyroidism was eventually controlled with an ablative dose of 1311. Thyroid hormone will be given in an attempt to suppress her TSH.

Effects of Thyroid Hormones (T4, T3), Bromocriptine and Triac on Inappropriate TSH Hypersecretion

“…Nevertheless, the long-term treatment with bromocriptine was not associated with lowered serum TSH levels or a reduced TSH response to TRH. The same has also been noticed in some (Beck-Peccoz et al, 1983;Sriwatanakul et al, 1984), although not in all previous reports on similar patients (Spitz et al, 1984;Takamatsu et al, 1984). The discrepancy between acute and chronic effects of bromocriptine in our patients remains unexplained.…”

TSH Producing Pituitary Tumor:

“…This difficulty in differentiating tumor from non-tumorous TSH secretion is not unique to this case. Spitz, Glaser, Scheinfeld and Hirsch (1984) described a case of isolated non-tumorous inappropriate TSH secretion on the basis of a normal molar TSH/alpha subunit ratio, elevated responsiveness of TSH to TRH and a blunted TSH response to TRH during treatment with T3. The patient was later found to harbor a pituitary tumor which grew to more than 1 cm in diameter before it was recognized and resected (Glaser, personal communication).…”