Responsiveness of growth hormone-deficient children to human growth hormone. Effect of replacement therapy for one year.

Previous studies have shown that growth hormone (GH)-deficient children are more responsive to exogenous human growth hormone (HGH) than non-GH-deficient children. In six GH-deficient children, velocity of linear growth was less than 2.5 cm/yr. By the metabolic balance study technique, anabolic responses (increments in elemental balances) were measured to a 7 day course of 0.0532 U HGH/kg body weight (BW)(3/4) per day (dose B) and to 0.168 U/kg BW(3/4) per day (dose C). They were then treated for 1 yr with HGH at a dose intermediate between B and C. Velocity of linear growth accelerated to 15-25 cm/yr for the first 4-7 mo, then declined to 0-8 cm/yr. At 12 mo, responsiveness to doses B and C was measured again; the responses were only 20-60% as great as before treatment. After 3 mo without HGH treatment, responsiveness to the anabolic effects of doses B and C returned to the magnitudes observed before treatment. A low titer of plasma antibodies to HGH was detected in two of the six children at the end of the year's treatment; these titers showed little change after 3 mo without HGH. Thus the hyperresponsiveness of GH-deficient subjects to exogenous HGH, compared to non-GH-deficient individuals, declines during long-term HGH treatment and is restored by 3 mo interruption of treatment. These changes in peripheral responsiveness may be related to the decline in velocity of linear growth which occurs after 4-7 mo of continuous treatment. When HGH was withdrawn after 12 mo, all six patients exhibited negative balances of N, P, Na, and K and loss of BW. Ratios of elemental balances showed about half the weight loss to represent protoplasm, and about half extracellular fluid. These observations indicate a role of GH in the continuing regulation of nitrogen and mineral metabolism in addition to its function as a growth-promoting hormone.

[A case of GH and TSH secreting pituitary macroadenoma]. / Przypadek makrogruczolaka przysadki wydzielacego hormon wzrostu i tyreotropin.

A case of GH and TSH secreting pituitary macroadenoma is reported. A 45-year-old female presented clinical features of acromegaly (the abnormal growth of the hands and feet, with lower jaw protrusion), diabetes mellitus, hypertension, nodular goiter and hyperthyroidism of unclear origin. NMR pituitary imaging revealed intra and extrasellar tumor. The laboratory examinations showed very high plasma levels of GH and IGF-1 and normal level of TSH coexisting with high plasma levels of free thyroid hormones. Pharmacological pretreatment with somatostatin analogues caused the substantial reduction of GH and TSH plasma levels. Histological and immunohistochemical examination of the tissue obtained at transsphenoidal surgery showed GH and TSH secreting adenoma. The laboratory examinations after surgery showed normal GH and IGF-1 plasma levels and reduced insulin requirement, what indicates radical operation. The very low plasma levels of TSH and free thyroid hormones after surgery and immunohistochemical examination suggest central hyperthyroidism due to TSH secreting pituitary tumor (thyrotropinoma).

Infertility in patients with hyperprolactinemia from a pituitary adenoma. Effect of transsphenoidal pituitary adenectomy.

Four patients with infertility caused by a prolactin-secreting pituitary adenoma underwent transsphenoidal pituitary adenectomy. Preoperatively, in three patients prolactin level was elevated and gonadotropin levels were depressed. In one patient, prolactin level was elevated, and gonadotropin levels were normal, although no rise in gonadotropin levels was noted after clomiphene citrate therapy. In another patient growth hormone level was elevated. Pituitary function was otherwise normal in all patients. The patients underwent transsphenoidal pituitary adenectomy and postoperatively the first three showed normal prolactin and growth hormone levels. The fourth has not yet been reevaluated. Spontaneous pregnancy occurred in all four patients without manipulation shortly after surgery. We suggest that transsphenoidal pituitary adenectomy is a successful and low-risk approach to infertility secondary to prolactin-secreting pituitary adenomata.

Hypothyroidism secondary to biologically inactive thyroid-stimulating hormone secretion by a pituitary chromophobe adenoma: recovery after removal of the tumor.

A 50-year-old man, suffering from a large pituitary adenoma and panhypopituitarism, was found to have severely elevated thyrotrophin (thyroid-stimulating hormone [TSH]) levels (greater than 20.2 microunits/mL). The thyroxine (T4) level was low (less than 3.0 micrograms/dL). Thyroid sodium iodide I 131 uptake was low (5% at 24 hours). A TSH test result was normal, with a 24-hour 131I uptake of 52% and a normal-looking thyroid gland on scintiscan. After surgical removal of the pituitary chromphobe adenoma, T4 levels returned to normal (6.8 micrograms/dL) and TSH levels improved substantially (9.0 microunits/mL). Findings from repeated 131I uptake tests were normal (22% at 24 hours). Other pituitary functions improved also. These results suggest that the patient had biologically inactive TSH produced by the tumor. Removal of the tumor probably enabled recovery of the active TSH with the return of normal thyroid uptake and T4 production. Whenever hypothyroidism and high levels of TSH coexist with pituitary dysfunction, a TSH test is needed to distinguish between primary hypothyroidism and hypothyroidism secondary to biologic inactive TSH.

Cushing's disease in a patient with a 'nonfunctioning' pituitary tumor. Spontaneous development and remission.

A 40-year-old woman had visual loss and a large nonfunctioning pituitary tumor. After partial surgical resection and radiation treatment, clinical and biochemical evidence of Cushing's disease developed. The pituitary source of her adrenocorticotropic hormone hypersecretion was documented on selective venous sampling. After 18 months of medical therapy with metyrapone and aminoglutethimide, the patient experienced a spontaneous remission of her hypercortisolism. A "nonfunctioning" pituitary tumor has a hypersecretory potential.

[The strange case of a patient affected by acromegaly with osteoporomalacia without hypogonadism]. / Lo strano caso di un paziente affetto da acromegalia con osteoporomalacia senza ipogonadismo.

Acromegaly is a rare disease that, in the majority of cases, is due to the presence of a benign growth hormone (GH)-producing tumor of the pituitary. Growth hormone has profound effects on linear bone growth, bone metabolism, and bone mass. In acromegaly, the skeletal effects of chronic GH excess have been mainly addressed by evaluating bone mineral density (BMD). Most data were obtained in patients with active acromegaly, and apparently high or normal BMD was observed in the absence of hypogonadism. The Autors describe a case of patient affected by acromegaly without hypogonadism with serious osteoporosis and biological signs of osteomalacia.

Cushing Disease After Treatment of Nonfunctional Pituitary Adenoma: A Case Report and Literature Review.

We describe a very rare case of nonfunctional pituitary adenoma (NFPA) that exhibited corticotrophic activity after resection and radiotherapy. The possible mechanisms of the transformation from NFPA to Cushing disease (CD) are discussed.A 43-year-old man presented with impaired vision, bilateral frontal headaches, and hyposexuality. He had no symptoms suggestive of hypercortisolism, and 8 am plasma cortisol concentration was 67.88 ng/mL. Brain imaging revealed a 15 × 15 × 21-mm sellar mass suggestive of a macroadenoma. The tumor was resected by transsphenoidal surgery and identified by immunohistochemical analysis as a chromophobic adenoma that did not stain for pituitary hormones. The patient was treated with prednisone and levothyroxine replacement therapy. After a third recurrence, the patient presented with clinical features and physical signs of Cushing syndrome. Plasma adrenocorticotropic hormone (ACTH) and cortisol concentrations were elevated, and there was a loss of circadian rhythms. Inferior petrosal sinus sampling after desmopressin showed the central-peripheral ACTH ratio was greater than 3:1. A repeat transsphenoidal resection was undertaken. Immunohistochemistry revealed ACTH positivity. Three months following surgery, imaging showed little residual tumor, but plasma ACTH remained elevated. He was referred for postoperative Gamma Knife radiotherapy.The immunological activity and biological features of the hormones secreted from a pituitary adenoma vary with time. Because long-term outcomes are unpredictable, postoperative follow-up is essential to detect postoperative transformation from NFPA to CD.

Thyrotoxicosis and a thyrotropin-secreting pituitary tumor causing unilateral exophthalmos.

Hyperthyroidism due to a TSH-secreting pituitary tumor has been noted by a number of investigators. We describe a unique case in which a 17-yr-old female presented with clinical hyperthyroidism, a goiter, and unilateral exophthalmos. Serum T4, free T4, and T3 (RIA) were consistently elevated along with elevated TSH levels (range, 10-100 microunits/ml). Skull x-rays and computed tomography scan revealed a tumor invading the right orbit. Other pituitary function studies were normal and LATs was undetectable. Surgery performed resulted in 70% removal of the pituitary tumor and confirmed the presence of tumor infiltration into the right orbit. TRH tests done pre- and postoperatively (patient still clinically hyperthyroid with elevated T4 and TSH levels) showed TSH and PRL responsiveness. Electron microscopy of the tumor demonstrated features typical of pituitary thyrotrophs. Monolayer cultures of pituitary cells released TSH over time into the media but did not respond to TRH stimulation. Pituitary adenoma tissue content of immunoreactive TSH was 65 microunits/g wet tissue and demonstrated immunosimilarity with human standard. We conclude that the patient had a TSH-secreting pituitary tumor responsive to TRH stimulation.

Pituitary hyperthyroidism. Case report and review of the literature.

A 58 year old woman with an enlarged sella turcica was found to have hyperthyroidism with a supranormal concentration of serum thyrotropin. Transsphenoidal microsurgery resulted in the removal of a chromophobe adenoma comprised mainly of thyrotropes. Postoperatively, serum thyrotropin, thyroxine and triiodothyronine levels fell within normal limits, and the patient maintained normal thyroid and pituitary function.

Multiple endocrine adenomas in a patient with the Maffucci syndrome.

A patient with multiple cutaneous hemangiomas and skeletal dyschondroplasia (the Maffucci syndrome) was found to have a pituitary chromophobe adenoma, a parathyroid adenoma and two other neoplasms. The presence of two endocrine tumors suggested the syndrome of multiple endocrine adenomatosis, and raised the issue of an etiologic relationship between this disease and the Maffucci syndrome. Dyschondroplasia, however, has no known influence on the secretion of parathyroid hormone or any of the pituitary hormones. The Maffucci syndrome is associated with a high incidence of malignancy, but it involves primarily mesodermal derivatives whereas multiple endocrine adenomatosis affects tissues of ectodermal origin. The association of the two in our patient is probably fortuitous.

Mammary duct ectasia and pituitary adenomas.

Mammary duct ectasia developed in three postmenopausal patients who had had pituitary chromophobe adenomas. The first patient had bilateral duct ectasia that developed 8 and 11 years after hypophysectomy. The second patient, who also had bilateral ectasia, had a prolactin-producing pituitary adenoma for which bromocriptine was prescribed. The ectasia developed in one breast before commencing bromocriptine therapy, and in the other breast 2 years later. The third patient also had a prolactin-producing pituitary adenoma. Unilateral duct ectasia developed while bromocriptine was taken. The ectasia in all patients was very marked and affected all excised ducts. Cholesterol granulomas were sometimes very extensive. These cases suggest a relationship between certain hypothalamic/pituitary disorders, possibly related to prolactin secretion and the development of mammary duct ectasia in postmenopausal patients.

Suprasellar tumors and incidental optic disc anomalies. Diagnostic problems in two patients with hemianopic temporal scotomas.

Anomalous optic discs may be associated with relative temporal visual field defects that need to be distinguished from bitemporal field defects of chiasmal compression. Two patients with both anomalous discs and suprasellar tumors were hospitalized with temporal hemianopic scotomatous visual field defects. A 19-year-old woman with a chromophobe adenoma had a monocular temporal hemianopic scotoma in the eye exhibiting an inferior-nasal disc crescent. A 22-year-old man with a hypothalamic-chiasmal germinoma causing bitemporal hemianopic scotomas had minor disc colobomas bilaterally. Careful study of the optic discs and posterior fundus, as well as evaluation of the characteristics of the temporal field defects, should distinguish chiasmal compression in the occasional case where suprasellar tumor and anomalous optic discs coincide.

Unusual visual symptoms.

Three cases with unusual and interesting symptomatology are presented. In each case the symptoms alone can lead the physician to an accurate localization of the lesion.

Endocrinological associations of pituitary tumors.

The patient presented with poor vision (particularly OS) which had declined progressively over ten years. He had had bifrontal headaches over the past two years. Examination and visual field testing showed optic atrophy and a bitemporal hemianopia. Procedures leading to the diagnosis of pituitary adenoma are discussed, as are treatment modalities and association of pituitary adenomas with other entities.

Gonadotropin response to luteinizing hormone releasing hormone administration in secondary amenorrhea and galactorrhea syndromes.

Luteinizing hormone releasing hormone (LHRH), 100 mug, was administered to 60 patients with secondary amenorrhea. No side effects or adverse reactions occurred. Delayed FSH and LH peak outputs were observed in patients receiving LHRH subcutaneously rather than intravenously, but responses were otherwise comparable. The majority of patients with secondary amenorrhea had responses which fell into the 95% confidence limits of responses for normal ovulating women. Responses of patients with different forms of dysfunction may be similar, and patients with similar pathology may respond quite differently. The LHRH stimulation test may assist in the diagnosis of particular hypothalamic, pituitary, or gonadal dysfunction, but it must be used clinically in the context of a carefully integrated study.

Acute visual loss during pregnancy after bromocriptine-induced ovulation. The elusive tumor.

The evaluation of patients complaining of amenorrhea with or without galactorrhea has been greatly enhanced by the availability of serum prolactin determinations and advances in diagnostic radiology. Likewise, the treatment of these patients with ergot derivative has resulted in the return of normal menses, and many pregnancies have been reported. The present report is of a patient with hyperprolactinemic amenorrhea-galactorrhea successfully treated with bromocriptine. A pregnancy followed resumption of menses, and a suprasellar cromophobeadenoma became manifest by producing blindness of the patient. The case is presented with recommendations for diagnosis and treatment.

Delayed diagnosis of pituitary tumors.

Of 38 patients with presumed or proven pituitary adenomas, 24 first presented with ocular complaints. Of these, ten patients had a physician-caused delay in the formulation of the correct diagnosis. Reasons for the physician-caused delay in diagnosis include inadequate history evaluation, failure to perform adequate testing, provide follow-up examination, and recognize typical signs of pituitary adenomas.

Nasal visual field loss with intracranial lesions of the optic nerve pathways.

Five patients developed nasal visual field defects as a result of involvement of the intracranial portion of the optic nerves. The cause in each patient, respectively, was as follows: (1) dolichoectatic carotid arteries, (2) optochiasmatic arachnoiditis, (3) meningioma of the olfactory groove, (4) pituitary apoplexy, and (5) pituitary chromophobe adenoma. The common factor in these cases was probably impaired circulation in the prechiasmal arterial anastomotic network. The nasal visual field loss present in these cases was characterized by a pattern similar to that seen in glaucoma but with impairment of visual acuity. The superior nasal visual field was usually normal and the lower temporal visual field often defective.

Abscess formation within pituitary tumors.

Three consecutive cases where abscesses were found within pituitary tumors are presented. In all cases, the diagnosis was made preoperatively and the patients were begun on stress doses of hydrocortisone and antibiotics before surgical drainage of the abscess. All patients recovered with minimal neurological deficits. Review of the literature reveals that the diagnosis is seldom made preoperatively or before autopsy and is associated with high mortality and morbidity. Early suspicion of a pituitary abscess leading to early treatment with antibiotics and operative drainage seem to be important factors in decreasing this high mortality and morbidity.

Oral contraceptive history as a risk indicator in patients with pituitary tumors with hyperprolactinemia: a case comparison study of twenty patients.

This report presents a retrospective case comparison study of 20 hyperprolactinemic patients with pituitary adenomas treated at the Mount Sinai Hospital (1976-1079). An association between oral contraceptive (OC) use and 20 subjects with pituitary tumors was substantiated using discordant paired analysis. The comparison group consisted of appendectomy patients admitted during the same time period and matched for sex and age. The estimated relative risk was 4.0 (P less than 0.025). This study suggests that there is a significant association between OC use and pituitary tumors associated with hyperprolactinemia.

PIP: A retrospective case-comparison study of 20 hyperprolactinemic patients with pituitary adenomas is presented. Cases were from the period 1976-1979. Using discordant paired analysis, an association between oral contraceptive use and 20 subjects with pituitary tumors was substantiated. For comparison, a group of appendectomy patients admitted during the same time period and matched for sex and age was studied. An estimated relative risk of 4 (P .025) was found based on this comparison, and it is concluded that a significant association between use of oral contraceptives and pituitary tumors associated with hyperprolactinemia is suggested.