The simultaneous occurrence of acromegaly, hyperthyroidism and hyperparathyroidism is extremely rare and even that of acromegaly and hyperparathyroidism very unusual. Chromophobe adenomata producing either acromegaly, Cushing's syndrome or hyperthyroidism have been described in a limited number of cases. A unique case of a patient with acromegaly, hyperthyroidism and hyperparathyroidism and a chromophobe pituitary adenoma was studied. In the blood an unusually high level of thyrotrophin (TSH) was found (about 2 mU/ml) but no »long-acting thyroid stimulator« (LATS). The TSH activity remained unaffected by thyroidectomy and by treatment with triiodothyronine but was not found in the blood after surgical hypophysectomy. The pituitary tumour contained TSH only about 20 mU/209 mg weight of tissue, i. e. less than is found in normal human pituitary glands. There was evidence of inadequate secretion of corticotrophin and gonadotrophins. The evidence suggests that both the acromegaly and the hyperthyroidism were caused by increased production of growth hormone (STH) and TSH by the pituitary tumour. The hyperparathyroidism was due to a parathyroid adenoma. In four other acromegalic but euthyroid patients no TSH or LATS activity could be detected in the blood. In these patients the protein-bound iodine (PBI), free thyroxine and triiodothyronine-Sephadex uptake tests were normal. In addition in one of these patients, hyperparathyroidisni due to a parathyroid adenoma was observed. The occurrence of a parathyroid adenoma in acromegaly may be one facet of the multiple endocrine adenoma syndrome. In all 5 subjects the hydroxyproline in serum and urine was increased.

Inappropriate TSH hypersecretion was diagnosed in a 38-year-old woman (case 1) and in a 38-year-old man (case 2). Both of them had earlier been treated by ablative therapy for hyperthyroidism. The present diagnosis was based on elevated basal serum TSH levels despite elevated serum free thyroid hormone levels. Both of them had exaggerated TSH responses to TRH (peak value 240 mU/l in case 1 and 408 mU/l in case 2). Their albumin and prealbumin levels were normal. The serum TBG level was normal in case 1 but was elevated in case 2. Serum levels of alpha-subunits of TSH, and pituitary CT scans were normal. Despite mild clinical hyperthyroidism, peripheral indices of thyroid hormone action were normal. They had also relatives with apparent resistance to thyroid hormones. In view of the possibility that prolonged pituitary thyrotrophic stimulation is detrimental, various therapeutic approaches to suppress TSH levels were tried. Both T3 and T4 treatments lowered serum TSH levels, but were poorly tolerated. Acute administration of L-dopa or bromocriptine reduced serum TSH levels, but this was not seen during long-term therapy. TRIAC treatment lowered serum TSH levels, and the drug was well tolerated. Serum TSH responses to TRH were not blunted during T3, T4 or TRIAC treatments. Somatostatin also reduced serum TSH levels, but did not potentiate the effect of low dose T3 therapy. Our results suggest that the patients had unbalanced pituitary and peripheral thyroid hormone resistance, predominantly at the pituitary level. Of the drugs studied, TRIAC seemed to be the most suitable therapy.

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