On the mechanism of the inhibition of compensatory ovarian hypertrophy by goitrogens.
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In an attempt to assess a possible relationship between pituitary size and TSH secretion, the volume of sella turcica was measured in 570 subjects, 26 primary hypothyroid patients, and 34 thyrotoxic patients. The volume of sella turcica, measured by a 3-dimensional approach, increased progressively with age until 20 years of age and was rather constant thereafter in normal subjects. In thyrotoxic patients, the volume of sella turcica was normal in spite of decreased plasma TSH concentration. In contrast, 81% of primary hypothyroid patients had an abnormal enlargement of the sella turcica. The magnitude of an increase of sella turcica inversely related with a decrease in serum T4 and T3 concentrations. On the other hand, the magnitude of an increase of sella turcica correlated well with an increase of circulating TSH. We suggest that an increase of sella turcica indirectly reflects an increase in pituitary size and TSH-secreting capacity, possibly due to hypertrophy and hyperplasia of TSH cells in primary hypothyroid patients.
An osmoregulatory role for prolactin (PRL) in man has been postulated, and PRL secretion has been reported to be influenced by osmotic stimuli. Clinical observation, however, does not support this notion. The effects of water loading, hypertonic saline infusion and nicotine on serum PRL and on renal water metabolism were investigated in 6 normal subjects and in 8 patients with chronic hyperprolactinemia (four with and four without demonstrable pituitary tumors). None of the patients had thyroid, adrenal or vasopressin deficiency. Renal walter handling in these patients was indistinguishable from normal. Likewise, serum PRL was not affected by the stimuli employed in either the normal subjects or the patients. No correlation between degree or duration of hyperprolactinemia and renal water metabolism was found. It is concluded that PRL is not an important osmoregulatory hormone in man.
Fifteen female patients with amenorrhea and hyperprolactinemia were studied 1 to 3 times daily during the first 4 days of treatment with bromocriptine (2.5 mg b.i.d). Normal PRL levels were reached within one day in 12 while the mean value for the whole group showed no further significant decrease. Estradiol, LH and FSH levels did not vary significantly at this stage even in those 10 patients who subsequently resumed menstruation.
It has been shown that GH excess is associated with decreased leptin levels and decreased body fat mass. Reports regarding the effect of GH on serum leptin levels are inconsistent. We studied leptin secretion in 20 acromegalics before and 2 months after trans-sphenoidal surgery and in 20 gender-, age-, and body mass index (BMI)-matched control subjects. The mean 8-h leptin concentration for each subject was measured from a pool formed of samples collected hourly beginning at 2200 h until 0600 h the next morning. In a subgroup of 10 acromegalics, leptin pulsatility was assessed for the same period of time in 10-min sampling intervals. Basal GH, insulin-like growth factor-I (IGF-I), insulin, glucose, and lipids levels were measured. Area under the curve for insulin (AUCins) during oral glucose tolerance test was calculated. Control subjects and acromegalics had similar BMI, but patients with active acromegaly had significantly lower mean leptin level (mean +/- SEM; in men, 2.6+/-0.4 vs. 7.1+/-1.1 microg/L, P = 0.003; in women, 16.0+/-3.4 vs. 23.5+/-3.1 microg/L; P = 0.036). Mean 8-h leptin correlated with BMI (r = 0.57, P = 0.007, in controls; r = 0.70, P = 0.001, in patients). In stepwise regression analysis with mean 8-h leptin as a dependent variable, BMI (P<0.001) and gender (P = 0.01) in acromegalics entered the equation, whereas in control subjects gender, free fatty acids, insulin, and age accounted for 99.3% in leptin variability. After surgery, BMI did not change significantly; and glucose (P = 0.014), GH (P<0.001), and IGF-I (P<0.001) levels together with AUCins (P = 0.002) decreased, whereas mean leptin concentration rose significantly and attained normal levels (4.1+/-0.8 microg/L, P = 0.028) in acromegalic men and (23.6+/-4.7 microg/L, P = 0.003) in acromegalic women. Correlation between leptin level and BMI was preserved after surgery (r = 0.62, P = 0.005). In stepwise regression analysis, free fatty acids (P = 0.04) contributed to 26.8% of the variance in corrected-leptin (for BMI and gender). Leptin concentration peak height and interpeak nadir level rose significantly (P = 0.033 and P = 0.037) after surgery by Cluster analysis, without significant changes in leptin pulse frequency and incremental peak amplitude. Nocturnal rise of leptin (mathematically described by a cubic curve) was characterized by an acrophase just after midnight, before and after surgery. The amplitude and the average leptin concentration of the cubic fit increased significantly after surgery (P = 0.028 and P< 0.001). In conclusion in acromegalic patients: 1) leptin secretion maintains the pulsatility and nocturnal rise; 2) the gender-based leptin differences are preserved; 3) GH-IGF-I normalization leads to a rise in leptin that is not related to changes in BMI; and 4) the possible role of rise in leptin levels when assessing clinical and metabolic outcome of therapy in acromegalic patients deserves additional studies.
Bilateral adrenalectomy is indicated for the treatment of ACTH-dependent Cushing's syndrome when the tumorous source of ACTH hypersecretion cannot be identified or removed. Potential advantages of laparoscopic over open adrenalectomy include shorter hospitalization, decreased requirement for postoperative analgesia, and decreased postoperative morbidity due to incisional complications. Bilateral laparoscopic adrenalectomy performed for the treatment of ACTH-dependent Cushing's syndrome was attempted in 19 patients at our institution between 1995 and 1998. Conversion to an open procedure was required in three patients. All patients who underwent bilateral laparoscopic adrenalectomy were subsequently followed to assess the outcome of this intervention. Twelve patients with pituitary-dependent Cushing's syndrome and four with ectopic ACTH syndrome underwent successful bilateral laparoscopic adrenalectomy. All patients experienced resolution of the signs and symptoms (e.g. proximal myopathy, hirsutism, and emotional lability) of Cushing's syndrome as well as weight loss, improved glucose tolerance, and improved control of blood pressure. No residual cortisol secretion was detected in the patients. Bilateral laparoscopic adrenalectomy is a safe and effective treatment for Cushing's syndrome when the ACTH-secreting neoplasm cannot be removed.
Mutations of the PROP-1 gene cause combined pituitary hormone deficiency. Progressive ACTH/cortisol insufficiency is found in a few patients. Congenital hypoplasia of the anterior pituitary gland is the most common magnetic resonance imaging finding in patients with PROP-1 mutations. We present two brothers with compound heterozygosity for the two mutations 150delA and 301-302delAG of the PROP-1 gene. Both showed combined pituitary hormone deficiency of GH, TSH, PRL, and gonadotropins, as is typical for PROP-1 deficiency. We observed a developing insufficiency of ACTH and cortisol secretory capacity in both patients. Computed tomography revealed an enlarged pituitary in the older brother at 3.5 yr of age. Repeated magnetic resonance imaging after 12 yr showed a constant hypoplasia of the anterior pituitary lobe. Similarly, magnetic resonance imaging of the younger brother showed a constant enlargement of the anterior pituitary gland until 10 yr. At the age of 11 yr, the anterior pituitary was hypoplastic. The reason for pituitary enlargement in early childhood with subsequent decrease in pituitary size is not known. We speculate that altered expression of early transcription factors could be involved. Because both patients have the same PROP-1 mutations and an identical pattern of combined pituitary hormone deficiency, we suggest that early pituitary enlargement may be the typical course in such patients in whom pituitary surgery is not indicated.
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Osteoporosis is the most common complication of Cushing's syndrome. We retrospectively examined the prevalence and risk factors for osteoporosis in 42 female patients with Cushing's syndrome. Osteoporosis and atraumatic fractures were assessed by bone mineral density of the lumbar vertebral spine (L2-L4) using dual energy X-ray absorptiometry (DXA) and X-ray examination. The prevalence of osteoporosis and fracture were 54.8% and 21.4%, respectively. The prevalence of osteoporosis (69.6% vs. 37.8%) and atraumatic bone fracture (26.1% vs. 15.8%) were significantly higher in patients with adrenal Cushing's than in those with pituitary Cushing's. AP and lateral BMD was significantly higher in patients with pituitary origin than in those with adrenal origin. Among several variables examined by multiple logistic regression, the etiology of Cushing's syndrome (adrenal vs. pituitary origin) was a significant factor affecting the prevalence of osteoporosis. Neither age, body mass index, duration of amenorrhea, nor extent of hypercortisolism were significant factors in this analysis. Plasma DHEA-S and urinary 17-KS excretion were significantly higher in pituitary Cushing's than in adrenal Cushing's. The present study shows that the prevalence of osteoporosis in patients with Cushing's syndrome is influenced by its etiology. A factor associated with pituitary Cushing's syndrome, such as adrenal androgen, may protect these patients from glucocorticoid-induced osteoporosis.
OBJECT: Surgical and medical therapies successfully achieve biochemical remission in the majority of patients with secretory pituitary adenomas. Nevertheless, continued hypersecretion after first-line therapy occurs and requires adjunctive therapy to prevent morbidity and premature mortality. For patients in whom medical and surgical therapy have failed, gamma knife surgery (GKS) is performed with the goal of controlling tumor growth and excess growth hormone (GH) production. The authors report their experience with GKS in patients in whom surgical and medical therapies failed. METHODS: The neuroendocrine service at the University of Virginia has treated 220 patients with secretory adenomas. The authors evaluated the biochemical results in patients with acromegaly followed for greater than 18 months (64 patients) as well as those with Cushing disease (45 patients), Nelson syndrome (14 patients with adequate follow up [27 overall]), and prolactinomas (19 patients) followed for at least 12 months posttreatment. Biochemical remission occurred in 36% of patients with GH-secreting adenomas, 73% of those with Cushing disease, 14% of those with Nelson syndrome, and 11% of those harboring prolactinomas. Recurrence after biochemical remission was documented in four patients with Cushing disease. New hormonal deficits have occurred in 28% of patients with acromegaly, 31% with Cushing disease, 36% with Nelson syndrome, and 21% with prolactinomas. Minor visual deterioration developed in one patient with Cushing disease. CONCLUSIONS: Gamma knife surgery offers an important treatment modality in patients with secretory adenomas refractory to surgical and medical interventions.
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Syndromes of hypersecretion of pituitary hormone and sellar enlargement may on occasion be caused by a gangliocytoma instead of a pituitary adenoma. At least some of these rare tumors are apparently independent of and separable from the pituitary gland, its stalk, and the hypothalamus, and are therefore surgically removable without incurring further endocrine deficit. The authors report such a case, with successful removal of the tumor via a frontal craniotomy. The associated hypersecretion of pituitary hormone was corrected without disturbing normal pituitary function.