TSH-containing Pituitary Adenoma Associated with Primary Hypothyroidism Manifested by Amenorrhoea and Galactorrhoea

Abstract

The authors of this report describe a woman who had primary hypothyroidism associated with an ectopic (sublingual) thyroid and a pituitary adenoma, and who presented with amenorrhea and galactorrhea. Immunocytochemistry and ultrastructural examination were applied to the tumor. A 30-year-old woman was admitted to the hospital in January 1978 for menstrual irregularities, which she had had since menarche, and galactorrhea of 1 year's duration. She was placed on thyroid hormone replacement at the age of 2 months and took it regularly until she was 10 years old. Menarche occurred at 13 years of age. Because of reduction in the frequency of menses, she was started on cyclic oral ethinylestradiol (0.03 mg) plus levonorgestrel (0.1 mg) at the age of 27 years, with normal withdrawal bleeding. On suspension of the oral steroids, for the last 18 months, she became amenorrheic. Galactorrhea was diagnosed 1 year before admission. Since then, she has been treated with 120 μg of L-thyroxine and. 30 mg of L-triiodothyronine (T4 + T3) daily, but galactorrhea and amenorrhea persisted. At the age of 22 years, when the patient was off thyroid therapy, 2− and 24-hour neck 131I uptake by aberrant thyroid tissue was 6.5 and 19 per cent, respectively. The neck scintiscan revealed an ectopic (sublingual) thyroid. No stigmata of hypothyroidism were found, and the thyroid gland was not palpable. The breast had expressible milk, but the rest of the physical examination was normal. A lateral skull x-ray showed a slightly enlarged sella turcica with a double floor. Hypocycloidal polytomography of the pituitary fossa indicated thinning of the floor and localized erosion at the left of the midline, with a hemiation of soft tissue into the sphenoidal sinus. CAT-scan of the skull confirmed the presence of an intrasellar mass invading the left sphenoidal sinus. Pneumoenceph-alography did not show suprasellar extension of the tumor, and air did not enter the sellar cavity. Provocative tests of anterior pituitary hormones were performed when the patient had been euthyroid with T4 + T3 for 1 year without interruption. Basal LH and FSH were normal. The LH response to GnRH was increased, but the FSH response was normal. The GH and F responses to insulin-induced hypoglycemia were normal, as was the urinary 17-OHCS increase after metyrapone. There was no TSH response to TRH, but the serum TSH concentrations increased from 35 to a peak of 108 μU/ml after TRH, when the patient had been off thyroxine for 3 months, and serum T4 was below the normal range. Isolated serum prolactin before admission was consistently elevated, from 60–80 ng/ml on regular thyroid therapy, increasing when treatment was taken irregularly (140–180 ng/ml). Basal values were still increased when the patient had been on T4 + T3 for 1 year. There was a blunted response to TRH and chlorpromazine, either with or without thyroid replacement. In the same way, a decreased responsiveness to metoclopramide was observed. Prolactin decreased after L-dopa and bromocriptine. In July 1978, an invasive pituitary adenoma of the sphenoidal sinus was removed through the transsphenoidal route. Serum prolactin was 20 ng/ml 24 hours after surgery. Three months after surgery, with the patient on T4 + T3, the serum TSH responsiveness to TRH remained suppressed. Evaluation of prolactin secretion showed that, while the response to TRH remained blunted, the peak value after chlorpromazine decreased, and metoclopramide responsiveness became normal. The prolactin decrease with L-dopa and bromocriptine was normal. The patient when last seen in the outpatient clinic 2 years after surgery had regular menses, no galactorrhea, and a serum prolactin of 10 ng/ml on her usual T4 + T3 therapy. Light microscopy revealed a fairly cellular adenoma of small cells compactly grouped, forming irregular solid clumps devoid of architectural organization and with a rosette-like pattern in some areas. The abundant cyto