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[Acute hemorrhage and ischemic necroses in hypophyseal tumors: hypophyseal apoplexy].

Acute enlargement of pituitary adenomas due to haemorrhage or ischaemic necrosis in the tumour was described as "pituitary apoplexy" by Brougham et al. in 1950. Since then, more than 200 cases have been reported, but--especially in the German literature--the syndrome has caught only little attention. Therefore, in a series of 12 own patients, typical findings and clinical characteristics are demonstrated and the literature is discussed. 9 patients had a haemorrhage into the tumour, 3 an acute ischaemic necrosis. The guiding symptom was the acute onset with ophthalmoplegia (11 of 12 patients). Only in one case the adenoma was known before the apoplexy. Other symptoms were headache, blurred vision, drowsiness and, in severe cases, hemiparesis, coma, and hypothalamic disorder. Most important is the acute endocrinological substitution with hydrocortisone; this may be life-saving. Neuroophthalmological recovery depends on early operation: cases of oculomotor palsy require an operation within the first 2 weeks after the acute event. An emergency operation is required only by an acute amaurosis. In general there will be enough time for careful clinical endocrinological and radiological investigations.

Adenoma↗

[Neonatal hypoglycemia in congenital isolated aplasia of the adenohypophysis. A case report].

We report a female newborn with prolonged neonatal hypoglycaemia and vomiting. Endocrinologic studies demonstrated the absence of the anterior pituitary hormones ACTH, STH, LH, FSH, and PRL while TSH basal secretion as well as TSH stimulation were normal at the age of 2 months. Magnetic resonance imaging showed aplasia of the anterior pituitary and a nodular ectopic posterior lobe. Substitution with prednisone resulted in normalization of blood glucose values with clinical improvement of the patient. At the age of 8 months the patient was started on recombinant human growth hormone due to poor growth; with 10 months decrease of thyrotropin secretion resulted in additional thyroxine replacement therapy.

Body Height↗

[Initial symptoms and anamnestic time in 517 patients with pituitary adenoma].

OBJECTIVE: To find out whether recent techniques of investigating hypophyseal adenoma (computed tomography, magnetic resonance imaging and hormonal measurements) have brought about earlier diagnosis. PATIENTS AND METHODS: The time of onset of first symptoms and the duration from first symptoms to diagnosis (anamnestic time) were determined retrospectively from clinical, endocrinological, ophthalmological and localizing data on 517 patients (311 women, 206 men) with hypophyseal adenoma. RESULTS: The most common initial symptom was oligo- or amenorrhoea, in 57.9% of women, and disturbed libido or potency in 38.5% of men. Next most common were visual field deficits (women: 11.6%, men: 26.7%), signs of acromegaly (women: 11.3%, men 18.2%) and headaches (women: 11.3%, men 15.5%). The median anamnestic time in women, 3.0 years, was significantly longer than the 2.3 years in men (P < 0.001). In hormonally inactive adenoma the corresponding times were 2.0 years in women and 1.0 year in men; in prolactinoma 4.2 years and 2.0 years; in growth-hormone secreting adenoma 5.0 years and 5.5; and in ACTH-secreting adenoma 5.0 years and 1.0 year. CONCLUSIONS: Although diagnostic techniques have greatly improved, the anamnestic time for hypophyseal adenoma is not shorter than in earlier studies. This findings underlines the need for clearly directed history-taking and for good training in endocrinology.

Acromegaly↗

Results of treating childhood Cushing's disease with pituitary irradiation.

To determine the usefulness of conventional pituitary irradiation in childhood Cushing's disease, we reviewed the results of this treatment in 15 patients. Twelve were cured (mean plasma cortisol of less than 10 microgram per deciliter and 24-hour urinary 17-hydroxycorticosteroid excretion of less than 7 mg per gram of creatinine) within 18 months, and 10 of the 15 were cured within nine months. Three failures required bilateral adrenalectomy. Growth resumed in 12, with adult heights of 156 to 166 cm. Sexual development proceeded normally in all 15, with normal secondary sexual characteristics and sexual function, and demonstrated fertility in four married adults. Intellectual function appeared normal. Basal and stimulated hormone levels were normal, except for subnormal (5 ng per milliliter or less) growth hormone levels after hypoglycemia in one of 12 patients. There were no complications of therapy and no progressive pituitary enlargement or hyperpigmentation. Pituitary irradiation is safe and effective therapy for childhood Cushing's disease.

17-Hydroxycorticosteroids↗

Recovery of pituitary function after treatment with a targeted cytotoxic analog of luteinizing hormone-releasing hormone.

Recently, we developed a targeted cytotoxic analog AN-207 of luteinizing hormone-releasing hormone (LH-RH), consisting of an intensely potent derivative of doxorubicin, 2-pyrrolinodoxorubicin (AN-201) conjugated to carrier agonist [D-Lys6]LH-RH. In this study, we investigated the effects of cytotoxic analog AN-207, designed for targeted chemotherapy and radical AN-201 on pituitary function in rats. A selective damage to the pituitary gonadotroph cells was found at 1 week after a single i.v. injection of 150 nmol/kg AN-207, as evidenced by a 63% decrease in the LH-RH-stimulated release of LH in vitro. The release of growth hormone (GH) and thyrotropin (TSH), stimulated by GH-releasing hormone (GH-RH) and TSH-releasing hormone (TRH), respectively, was reduced by only 11-12%. In contrast, even a smaller dose of 75 nmol/kg of AN-201 nonselectively damaged pituitary function, reducing the stimulated release of LH, GH, and TSH by 57%, 74%, and 67%, respectively. Two weeks after administration, the LH-RH-stimulated LH release in vivo entirely normalized in the AN-207-treated rats, and only a 13% decrease in the LH response was found in the group given AN-201. GH and TSH responses to receptor-mediated stimuli with GH-RH and TRH were normal at 2 weeks in both treated groups. Neither cytotoxic compound caused changes in the concentration of pituitary LH, GH, or TSH, as determined by RIA at 1 week and 7 weeks after treatment. This study demonstrates that the cytotoxic LH-RH analog AN-207 exerts highly selective effects on the gonadotroph cells containing LH-RH receptors and is less toxic for other cells. Conversely, its cytotoxic radical AN-201 nonselectively damages the pituitary cells. The damaging effect of both cytotoxic compounds on pituitary functions is reversible. In view of its high selectivity and reduced toxicity, AN-207 could be a potential therapeutic agent for the treatment of tumors that possess receptors for LH-RH such as prostatic, mammary, ovarian, and endometrial cancers.

Animals↗

Effects of terguride on anterior pituitary function in parkinsonian patients treated with L-dopa: a double-blind study versus placebo.

In a randomized double-blind study, 20 parkinsonian patients (suffering from the disease for 2-18 years), chronically treated with levodopa (500-750 mg/day for 0.5-12 years), received terguride (1 mg b.i.d.) or placebo for 4 weeks. Growth hormone (GH), prolactin (PRL), thyroid-stimulating hormone (TSH), and insulin-like growth factor (IGF-I) secretions were studied before and after the morning dose of levodopa (250 mg p.o.), both before and at the end of study period. At the beginning of the study, basal hormonal levels were within normal limits, and levodopa administration induced a significant suppression in PRL and TSH levels (both p < 0.01)) and a significant increase in GH (p < 0.01). The same results were observed at the end of the study period in the placebo group. Addition of terguride induced a significant suppression in basal PRL levels (p < 0.01), whereas levodopa-induced hormonal changes were unaffected. These data suggest that the hypothalamic dopaminergic function that controls anterior pituitary hormones is preserved in parkinsonian patients, regardless of both the duration of the disease and the long-term treatment with levodopa. The strong additional prolactin-lowering effect of terguride indicates long-lasting dopaminergic effects, as is already known from hyperprolactinemic conditions. The dopaminergic effects of levodopa on TSH, GH, and IGF-I secretion were unchanged by terguride treatment. The anti-dopaminergic effects of terguride observed in the motor system in animal studies, as well as in levodopa-induced dyskinesias in parkinsonian patients, could not be observed in the case of the dopaminergic control of anterior pituitary hormones under the conditions of this study.

Aged↗

Identification of gonadotropin-releasing hormone in neurons of a hypothalamic hamartoma in a boy with precocious puberty.

We have studied a 3 1/12-year-old boy who presented with a hypothalamic mass and precocious puberty. His history suggested a course of isosexual precocity progressing from birth. Gelastic seizures also began at an early age. Endocrine evaluation revealed normal thyroid-stimulating hormone and growth hormone secretion, elevated basal and stimulated prolactin concentrations, and luteinizing hormone responses to sequential intravenous injections of gonadotropin-releasing hormone (GnRH) that were pubertal in pattern and magnitude. A needle biopsy of the mass recovered tissue that contained neurons histologically similar to those found in the normal hypothalamus, and the mass was characterized as a hypothalamic hamartoma. Immunohistochemical staining of this tissue with anti-GnRH antiserum demonstrated positive staining for GnRH immunoreactivity in neurons. This suggests a neurosecretory pathogenesis for the precocious puberty found in patients with hamartomas in the hypothalamic region.

Biopsy, Needle↗

Transnasal endoscopic surgery of the pituitary gland: technical note.

OBJECTIVE: An approach to transnasal transsphenoidal debulking of pituitary tumors using endoscopic guidance is presented. METHODS: Technical details of this approach using an endoscope inserted through one nostril and operating instruments inserted through a submucosal tunnel created via the other nostril are discussed. RESULTS: Ten patients who had operations are tabulated. Illustrative cases are presented. CONCLUSION: Endoscopic debulking of pituitary tumors can provide good results with minimal operative morbidity.

Adenoma↗

Transnasal microsurgery in children and adolescents with Cushing's disease.

OBJECTIVE: Transnasal adenomectomy is the treatment of choice for Cushing's disease. We review the diagnostic peculiarities, specific surgical problems, and outcome of children and adolescents with Cushing's disease. METHODS: We report on our series of 55 consecutive children and adolescents (range, 4.2-18.9 yr [mean age, 14.4 yr]; female:male = 1.1:1.0; mean follow-up, 54.5 +/- 38.6 mo [standard deviation]) with Cushing's disease on whom we performed surgery since 1980. The indication for transsphenoidal surgery is based on endocrinological parameters and not on neuroradiological findings. RESULTS: Detection rate of the tumor site was 22% using computed tomography and 33% using magnetic resonance imaging. Only 7 of 13 interpetrosal adrenocorticotropic hormone gradients obtained during inferior petrosal sinus sampling correctly lateralized the tumor site preoperatively (53.8%). In cases of incomplete sphenoid pneumatization, adequate exposure is achieved by drilling. The tumor finding rate is 98%. The remission rate is 100% when two early subsequent operations are included. The recurrence rate for 45 primary operations with follow-up of at least 1 year is 15.5%. Seven of nine subsequent operations for recurrent hypercortisolism were successful. One patient needed three more operations until hypercortisolism subsided; one patient achieved remission after additional pituitary irradiation. The surgical morbidity was low in this series, which consisted of two cerebrospinal fluid fistulas. The incidence of hypopituitarism after primary operations (10.3%) is significantly lower than after subsequent operations (45.5%). CONCLUSION: Direct transnasal submucosal surgery for Cushing's disease is successful, and pituitary function can be preserved in most of these young patients.

Adenoma↗

Clinically silent corticotroph tumors of the pituitary gland.

OBJECTIVE: To determine the clinical presentation, imaging characteristics, microscopic and ultrastructural characteristics, and treatment outcomes of patients with clinically silent pituitary corticotroph adenomas. METHODS: All silent corticotroph adenomas diagnosed at the Mayo Clinic during the years 1975 through 1997 were selected from the files of the Mayo Tissue Registry. RESULTS: We studied 23 cases, occurring in 16 male and 7 female patients (age range, 11-79 yr; mean age, 48 yr), who presented with headaches (50%), visual field defects (61%), extraocular muscle paresis (13%), hypopituitarism (26%), and galactorrhea/amenorrhea (43%/29% of the female patients). No patients exhibited clinical hypercortisolism. All tumors were macroadenomas (2.4+/-0.8 cm; range, 1.5-4.0 cm) and exhibited suprasellar extension in 87% of the cases and hemorrhage, necrosis, and/or cystic changes in 61%. All tumors stained were variably periodic acid-Schiff-, adrenocorticotropic hormone-, and beta-endorphin-positive, particularly Subtype I lesions. Ultrastructural classification was performed in 19 cases. In a comparison of Subtype I and II tumors, differences were observed with respect to sex (male/female, 1.4:1 versus 6:1), preoperative hyperprolactinemia (5 of 16 versus 0 of 6 cases), preoperative hypopituitarism (9 of 16 versus 5 of 7 cases), radiographic or gross invasion (7 of 16 versus 5 of 7 cases), and partial or total postoperative pituitary failure (6 of 16 versus 6 of 6 cases). The overall median postoperative follow-up period was 4.9 years (range, 0.3-16.6 yr); 54% of the patients had persistent or recurrent tumors. CONCLUSION: Clinically silent corticotroph adenomas behave in an aggressive manner and are characterized by the following: lack of clinical signs or symptoms of Cushing's syndrome and normal cortisol levels; no or only minor elevations of serum adrenocorticotropic hormone levels; macroadenomas with hemorrhagic infarction; and presentation dominated by mass effect symptoms. The high persistence/recurrence rate underscores the need for long-term follow-up.

Adenoma↗

Common disorders of the pituitary gland: hyposecretion versus hypersecretion.

An understanding of pituitary disorders requires much more than a knowledge of the definitions associated with them. To grasp fully their complexity, one must recognize not only the powerful role the pituitary gland plays in the endocrine system, but also its effects on homeostasis throughout the entire human body, its association with the hypothalamus, and ultimately its associated end organs. Because of the many hormones stored or produced by the pituitary, associated disorders often are confusing and challenging. However, by simplifying the classification of these disorders into the categories of hyposecretion and hypersecretion, the understanding of pituitary disorders is made simple, and the associated interventions become apparent.

Adrenocorticotropic Hormone↗