Pituitary gland enlargement in primary hypothyroidism: a report of 5 cases with follow-up data

Five female patients with primary hypothyroidism and radiological evidence of a pituitary enlargement were studied before and after a mean of 30 months (range 12-83 months) treatment with thyroxine (T4). Before treatment, serum thyroid-stimulating hormone (TSH) levels were elevated in every patient (mean 392 mU/l, range 240-475) and prolactin levels in 4 (mean 79 micrograms/l, range 48-143 micrograms/l). CT scanning confirmed the presence of pituitary enlargement in the 4 patients studied, which was suprasellar in 3. The remaining patient had an enlarged fossa on a lateral skull radiograph. During treatment with T4, TSH and prolactin levels were normal in all. Complete disappearance of the enlargement was seen on follow-up scans in all patients and 1 developed an empty sella. The induction of a pituitary enlargement by primary hypothyroidism results from reversible hyperplasia of both the TSH and prolactin-secreting cells in most instances. Occasionally, however, hyperplasia of the thyrotrophs can occur in isolation and an empty sella can occur after successful treatment with T4. Thyroid function tests should be obtained in all hyperprolactinemic patients.     

Coexisting acromegaly and primary empty sella syndrome

The normal functions of the pituitary gland may be suppressed when the gland is compressed onto the sella floor by arachnoid tissue extending through an impaired sella diaphragm. Interestingly, pituitary hormone hypo- and hypersecretion, including acromegaly, have been observed in patients with an 'empty sella'(1-4). This 'empty sella syndrome' has been classified into a primary form, in which no inciting factor (pituitary irradiation or surgery for a pituitary tumor) is present, and a secondary form, in which the empty sella occurs after pituitary procedures. In this report we describe a patient who presented with clinical and biochemical features of acromegaly and who had an empty sella on pituitary magnetic resonance imaging (MRI).     

Changes in plasma inhibin levels following pulsatile gonadotrophin-releasing hormone therapy in a man with idiopathic hypogonadotrophic hypogonadism

Changes in circulating inhibin levels were related to changes in testosterone (T) and the gonadotrophins luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in a hypogonadotrophic hypogonadal man before and during pulsatile gonadotrophin-releasing hormone therapy which resulted in normal spermatogenesis. Before treatment, the plasma inhibin levels in the patient (210 +/- 50 U/l; mean +/- SD of four samples) were lower than in normal controls (552 +/- 150 U/l; p less than 0.01), as were T (1.1 nmol/l) and gonadotrophin (less than 1.0 IU/l) levels. Within 1 week of gonadotrophin-releasing hormone treatment, plasma LH (14.1 +/- 0.7 IU/l) and FSH (14.4 +/- 0.6 IU/l) reached supraphysiological levels. In response, T and inhibin concentrations increased progressively to reach high normal levels (27.7 +/- 1.6 nmol/l and 609 +/- 140 U/l) at 4 weeks, by which time the gonadotrophin levels stared to decline and gradually returned to the normal range between 12 and 24 weeks of treatment. There was a concomitant decrease in T and inhibin levels which remained within the normal range. The decline in the FSH level following the rise in testicular hormones was earlier and steeper than that of LH (37.5% decrease at 4 weeks vs. 30.4% at 12 weeks), suggesting that T and inhibin may act together to inhibit pituitary FSH secretion as opposed to LH secretion which is primarily controlled by T. It is concluded that, in man, during maturation of the pituitary-testicular axis, changes in circulating inhibin parallel those of T, and quantitatively normal inhibin secretion is dependent on gonadotrophin stimulation. FSH secretion may be regulated through negative feedback control, by both T and inhibin.     

May primary empty sella turcica be a cause of isolated ACTH deficiency? A case report and the review of related literature

Isolated ACTH deficiency is an uncommon cause of secondary adrenocortical insufficiency and accompaniment with primary empty sella has been reported in several cases. We present a case of isolated ACTH deficiency associated with empty sella. A sixty-two year old woman was admitted to our endocrine clinic with complaints of weakness, fatigue, weight loss, nausea, vomiting, and lack of appetite for about one month. Physical examination indicated orthostatic hypotension and epigastric tenderness. Laboratory investigations revealed hypoglycemia, hyponatremia and anemia, in addition low plasma cortisole and ACTH levels. Serum cortisole responses to short and prolonged ACTH stimulation were tested and partial and accurate responses were obtained, respectively. Plasma ACTH and serum cortisole levels failed to respond after intravenous injection of human corticotropin releasing hormone. Other hypophysial hormone levels were within the normal reference ranges. Although cranial and abdominal computerized tomography images were evaluated as normal, cranial magnetic resonance imaging of the pituitary gland revealed 'primary empty sella turcica'. Replacement therapy with methylprednisolon resulted in the improvement of hypoglycemia, hyponatremia and clinical symptoms. Based on these results, the patient was diagnosed as isolated ACTH deficiency and was scheduled for follow up by our outpatient clinic. Our report is consistent with other reports pointing out that primary empty sella may be responsible for pathogenesis of isolated ACTH deficiency.     

Classical pituitary apoplexy presentation and a follow-up of 13 patients

Thirteen patients who presented with signs and symptoms of pituitary disease gave a history of classical pituitary apoplexy. Six presented with acute symptoms and in 7 the history antedated the admission by a mean of 887 days (range 365-2,190 days). All patients had an enlarged eroded sella. CT scans revealed a bleed in the tumor in 11 (histologically confirmed in all 8 patients operated), evidence of residual tumor in 1 and an empty sella (ES) in 1 patient. Hypopituitarism was present in 9, 4 were endocrinologically normal, 8 had visual problems requiring decompressive surgery and radiotherapy (RT) was given to 7 patients. They were subsequently followed for a median period of 730 days (range 365-3,385 days). During this time an empty sella developed in 5, 2 of whom had no surgery or RT; 4 remained endocrinologically normal, and a second hemorrhage occurred in 2 patients. Histological evidence of previous bleeds was noted in 6 of the 8 patients treated surgically. We conclude that apoplexy (1) may produce complete or partial tumor destruction with or without preservation of endocrine function; (2) recurrent, often silent, bleeding into a pituitary tumor appears to be a common event; (3) RT should be withheld unless recurrent tumor is documented (since at least 2 patients in this study have experienced spontaneous resolution of the tumor); and (4) the presence of an enlarged eroded fossa with an ES is reasonable presumptive evidence of an infarction of a pre-existing pituitary tumor.     

Effects of season and testosterone treatment on gonadotrophin secretion and pituitary responsiveness to gonadotrophin-releasing hormone in castrated Romney and Poll Dorset rams.

In castrated rams (Romney and Poll Dorset, n = 8 for each breed), inhibition by testosterone treatment (administered via Silastic capsules) of luteinizing hormone (LH) pulse frequency, basal and mean LH concentrations, mean follicle-stimulating hormone (FSH) concentration, and the peak and total LH responses to exogenous gonadotrophin-releasing hormone (GnRH) were significantly (P less than 0.01) greater during the nonbreeding than during the breeding season. Poll Dorset rams were less sensitive to testosterone treatment than Romney rams. In rams not receiving testosterone treatment, LH pulse frequency was significantly (P less than 0.05) lower during the nonbreeding season than during the breeding season in the Romneys (15.8 +/- 0.9 versus 12.0 +/- 0.4 pulses in 8 h), but not in the Poll Dorsets (13.6 +/- 1.2 versus 12.8 +/- 0.8 pulses in 8 h). It is concluded that, in rams, season influences gonadotrophin secretion through a steroid-independent effect (directly on hypothalamic GnRH secretion) and a steroid-dependent effect (indirectly on the sensitivity of the hypothalamo-pituitary axis to the negative feedback of testosterone). The magnitude of these effects appears to be related to the seasonality of the breed.     

Association of adverse perinatal events with an empty sella turcica in children with growth hormone deficiency

High-resolution computed tomography (HR-CT) of the hypothalamo-pituitary region was performed in 26 consecutive children presenting with growth hormone deficiency (GHD) at one clinic. 58% had an empty sella turcica (ES) and 42% a full sella turcica (FS). There was no difference between the ES and FS groups for mean (+/- 95% confidence limits) presentation age (ES 6.7 (+/- 1.8) years, FS 5.6 (+/- 2.2) years), height standard deviation score (SDS) (ES -3.9 (+/- 0.8), FS -3.3 (+/- 0.5] nor head circumference SDS (ES -1.9 (+/- 1.1), FS -0.7 (+/- 1.1]. There were significant associations between the ES group and a history of adverse perinatal events (p less than 0.001) and multiple pituitary deficiency (p = 0.014). Growth hormone response to an acute growth hormone releasing factor test showed no association with HR-CT diagnosis. Sella turcica volumes were calculated from the HR-CT scans. All sella volumes were small; mean SDS for height was -2.6 (+/- 0.2). There was no difference in sella volume SDS between the ES and FS groups (ES -2.9 (+/- 0.3), FS -2.5 (+/- 0.4]. Adverse perinatal events may cause an ES and GHD by compromising the blood supply to the pituitary gland or infundibulum.     

Empty sella following spontaneous resolution of a pituitary macroadenoma

BACKGROUND/AIM: Empty sella is a radiological finding characterized by the presence of arachnoid herniation into the sella, resulting in compression of the pituitary against the sella wall. The objective of this case presentation is to discuss secondary empty sella in a patient with spontaneous resolution of a pituitary macroadenoma. METHODS: A case of empty sella syndrome is presented. Static and dynamic testing was performed. Etiology, pituitary function, and imaging are discussed. RESULTS: A 69-year-old African-American woman was referred by her primary care physician for evaluation and treatment of 'hypothyroidisim'. Thyroid tests were performed because of muscle and joint tenderness and revealed low free thyroxine and normal thyroid-stimulating hormone levels. The diagnosis of secondary hypothyroidism was made, and magnetic resonance imaging (MRI) of the pituitary revealed an empty sella turcica. In retrospect, the patient had presented 11 years earlier with tinnitus, and an MRI of her auditory canals demonstrated an 'incidental' 1.5-cm pituitary tumor. No endocrine evaluation was done at that time, and neurosurgical follow-up of the pituitary tumor by serial MRIs demonstrated the genesis into empty sella. CONCLUSIONS: In our patient the natural history of her pituitary tumor was that it involuted and resulted in an empty sella. Although oftentimes speculated as a cause of empty sella, tumor involution has rarely been shown to be causative. In this instance, empty sella was associated with hypopituitarism. This case illustrates the importance of endocrine evaluation of patients with this radiological finding.     

Paradoxical prolactin response to growth hormone-releasing hormone in a patient with hyperprolactinemia and empty sella.

In a 30-year-old woman with amenorrhea due to hyperprolactinemia, serum PRL increased to twice the basal amount in response to growth hormone-releasing hormone (GHRH). Roentgenological studies revealed no pituitary adenoma but empty sella. Bromocriptine therapy normalized serum PRL and made the paradoxical response to GHRH disappear. The paradoxical response did not occur in any of eight other patients with hyperprolactinemia due to prolactinoma. Although this case is rare, GHRH stimulates PRL as well as GH release remarkably in some cases with hyperprolactinemia without a GH-producing tumor.     

Requirement of thyroid function for the expression of seasonal reproductive and related changes in red deer (Cervus elaphus) stags.

The effect of thyroid function on regulation of seasonal reproduction was investigated in three red deer stags thyroidectomized (THX) in summer (January 1988) in comparison with five thyroid-intact controls. Responses of luteinizing hormone (LH) and testosterone to a bolus injection of 10 micrograms gonadotrophin-releasing hormone (GnRH) were tested in July, October, December, February and April. Blood samples were collected at weekly intervals from December 1987 to June 1989 for measurement of testosterone, triiodothyronine (T3) and prolactin concentrations. Testis diameters were measured every 2 weeks. In October 1988 (spring), plasma LH concentrations of control stags were less responsive (P less than 0.01) to stimulation by GnRH than those of THX stags; plasma testosterone concentrations and testis diameters were low and there was no increase in plasma testosterone concentrations after injection of GnRH in control stags during October or December (spring, early-summer). In contrast, THX stags maintained a testosterone response (P less than 0.01) in these 2 months and did not exhibit any signs of a seasonal lack of reproductive activity at this time of year. Control stags cast antlers in spring whereas THX stags maintained hard antlers throughout the study. Concentrations of plasma T3 were not detected in THX stags from June 1988 onwards, but exhibited a seasonal pattern in control stags, with low concentrations during autumn and winter (April to July) and high concentrations in spring and summer (August to February). There was no effect of thyroidectomy on the seasonal pattern of prolactin secretion.(ABSTRACT TRUNCATED AT 250 WORDS)     

Empty sella in control subjects and patients with hypopituitarism

The frequency and distribution of various degrees of empty sellae have been examined in subjects without any pituitary disorder and in patients with hypopituitarism. Among them none had sellar enlargement. Sellar computed tomography (CT) with contiguous 2 mm slices (thickness in the axial projection) was performed in 56 control subjects. The CT findings on sella turcica were graded into 4 groups (0, 1+, 2+, and 3+), and grades 2+ and 3+ indicated moderate and marked empty sellae. Thirty-nine percent of the control subjects had empty sellae of grade 2+ or 3+. Sellar CT scans with contiguous 2 mm slices were also performed in 11 patients with hypopituitarism. The sellar volume ranged from 224 to 715 mm3. CT scan was carried out more than 2 years after the onset of hypopituitarism in 10 of 11 patients, and showed typical empty sellae of grade 3+ in all 10 patients. There was no empty sella in a patient with hypopituitarism whose CT scan was carried out 3 months after the massive postpartum hemorrhage. Our results indicate that moderate empty sella of grade 2+ can be seen in subjects without any pituitary disorder, and that a typical empty sella of grade 3+ is present in hypopituitarism with a normal sized sella turcica. An empty sella associated with hypopituitarism may be due to shrinkage of the pituitary gland related to its hypofunction.     

A patient with hypogonadotropic hypogonadism successfully treated by long-term pulsatile administration of luteinizing hormone-releasing hormone

A male patient with hypogonadotropic hypogonadism has been treated by pulsatile administration lf luteinizing hormone-releasing hormone (LHRH) (20-25 micrograms, every 2 hours, sc) for 4 years 6 months. His plasma testosterone (T) concentration began to increase after 4 weeks of treatment and reached the normal range in week 5. He showed complete secondary sexual development after 1 year of treatment. His sperm count was normalized after 1 year of treatment. He was married after 29 months of therapy, and has a healthy male child. Blood type tests showed his paternity of the child. During the long duration of pulsatile LHRH therapy, his gonadotropin secretion has been stimulated by LHRH and his T level has been maintained with no observable side effects. There are no other reports of patients treated by pulsatile LHRH injection for such a long duration, but finding in this patient indicated that long-term pulsatile LHRH therapy is a useful and safe method for treatment of hypothalamic hypogonadotropic hypogonadism.     

Changes of plasma lipids and lipoprotein levels during danazol treatment for endometriosis

Previous data of lipid and lipoprotein level changes with the application of danazol, an isoxazol derivative of 17-alpha-ethinyl testosterone, have been conflicting. We measured cholesterol, triglycerides, low density lipoproteins and high density lipoproteins, estradiol and progesterone in 62 patients treated for endometriosis with danazol 600 mg daily. The fasting blood samples were taken before, every month during danazol medication, and 4, 12 and 24 weeks after cessation of therapy. Inconsistent changes in total cholesterol and triglyceride levels were observed. The data showed a constant, though not significant increase of the mean LDL levels. Plasma HDL decreased approximately 45% during the first two months of danazol influence and remained constantly low for the rest of the treatment. The atherogenic ratio (LDL:HDL) was doubled by-danazol. Five patients developed a reversible type IIa hyperlipoproteinemia. The plasma levels of estradiol decreased, but showed normal midfollicular values during the treatment period. In contrast, the plasma levels of progesterone fell significantly and were sometimes undetectable. These findings demonstrate an atherogenic potential of danazol, especially when long term treatment is taken into consideration.     

Growth, bone maturation and height prediction after three years of therapy with the slow release GnRH-agonist Decapeptyl-Depot in children with central precocious puberty.

More than 100 patients with central precocious puberty are participating in this international multicenter study using monthly i.m. injections of the slow-release GnRH agonist Decapeptyl-Depot. In 15 patients, Decapeptyl-Depot treatment could be discontinued after 2 years of therapy. Gonadal suppression was promptly reversible in all of them, as shown by prepubertal low gonadotrophin- and sex steroid levels. Of the remaining 90 patients, 40 have been treated for more than 3 years, including 33 girls and 7 boys. Plasma levels of LH, FSH, estradiol and testosterone dropped to the prepubertal range after one month of Decapeptyl-Depot and remained there for the whole period of therapy. At start of therapy, mean chronologic age of these 40 children was 6.6 +/- 1.4 (SD) years, mean bone age 10.2 +/- 1.9 years. Mean predicted adult height increased in the boys from 173.6 +/- 13.8 (SD) cm at start of therapy to 184.6 +/- 17.0 cm after 3 years. Predicted adult height increased in girls from 158.0 +/- 12.2 to 161.0 +/- 7.5 cm. Undue side effects were not seen, long term tolerance was good. It is concluded that Decapeptyl-Depot injected i.m. every 4 weeks suppresses the pituitary-gonadal axis in children with central precocious puberty without clinical or biochemical escapes, and leads to an increase in predicted adult height by more than 3 cm in all boys and in 53% of the girls after three years of treatment.     

Sheehan syndrome: clinical and laboratory evaluation of 20 cases

Sheehan syndrome (SS) or post-partum pituitary necrosis is a pituitary insufficiency secondary to excessive post-partum blood losses. SS is a very significant cause of maternal morbidity and mortality in developing countries although it is a rarity in developed countries in which obstetrical care has been improved. In this study, we reviewed 20 cases retrospectively who were diagnosed as SS in our clinic. The patients aged 40 to 65 years with a mean age of 51.12 +/- 9.44 years (mean +/- SD). Time to make a definitive diagnosis of the disease ranged between 5 and 25 years with a mean of 16.35 +/- 4.74 years. Three of our patient (15%) had a previous diagnosis of SS. Three patients (15%) were referred to emergency service for hypoglycemia, three patients (15%) for hypothyroidism and one patient (5%) for hyponatremia. Dynamic examination of the pituitary revealed GH, Prolactin, FSH, TSH and ACTH insufficiency in all of the patients. One of our patients had a sufficient LH response to LHRH challenge. All of the patients were imaged with pituitary MRI. Eleven patients had empty sella and 9 patients had partial empty sella. SS is still a common problem in our country, especially in rural areas. Considering the duration of disease, important delays occur in diagnosis and treatment of the disease.     

Bone Marrow Hypoplasiaresponsive to Testosterone Therapyin a Patient with Panhypopituitarism:Need for Adherence to Androgen Replacement

ObjectiveTo describe the case of a young Saudi male patient with long-term panhypopituitarism and pancytopenia attributable to poor adherence to androgen replacement therapy, which resolved after institution of testosterone treatment and recurred after another interval of poor adherence to recommended therapy.MethodsWe present the clinical and laboratory data before and after treatment with testosterone. In addition, the corresponding histologic changes in the bone marrow are illustrated.ResultsAfter resection of a hypothalamic glioma, panhypopituitarism developed in a 14-year-old Saudi boy. At age 22 years, he had shunt-related meningitis. He was then noted to have pancytopenia, with a platelet count of 54 × 10³/μL, a hemoglobin concentration of 6.9 g/dL, and a leukocyte count of 2.7 × 10³/μL. After treatment of sepsis, the pancytopenia persisted. No underlying cause was detected. Bone marrow biopsy showed a hypocellular marrow with dysplastic megakaryocytes. The patient’s family indicated that he had not been taking his testosterone therapy. Testosterone decanoate (250 mg) was administered intramuscularly daily for 3 days. His platelet count increased to 74 × 10³/μL. Maintenance therapy with testosterone once weekly for 3 weeks and then once every 3 weeks resulted in improved hematologic findings. Repeated bone marrow biopsy after 6 weeks showed normocellular marrow, with disappearance of the megakaryocytic dysplasia. The patient again discontinued his testosterone treatment, and the hematologic abnormalities recurred but were again corrected after supervised testosterone therapy.ConclusionThis case emphasizes the importance of androgen replacement therapy in patients with hypopituitarism, not only for sexual potency, bone strength, and quality of life but also for normal bone marrow function. (Endocr Pract. 2008;14:229-232)     

The pituitary and testicular responses to GnRH challenge between 4 and 14 months of age in thoroughbred colts born in spring and autumn

Gonadotropin releasing-hormone analogue (buserelin) challenges were carried out every 8 weeks from 4 to 14 months of age on thoroughbred colts born in the spring (n = 6) or autumn (n = 5) to define the onset of puberty. In all colts, luteinizing hormone (LH) secretion followed a seasonal pattern, with high baseline and maximal concentrations in the spring and summer and low concentrations in the winter. Testosterone concentrations were undetectable before spring and, thus, autumn-born colts were younger than spring-born colts when a testosterone response to buserelin was first observed. Mean weights of the autumn-born colts were 300 kg (282-327 kg) at the time of the first detectable testosterone response in the following spring (October). Spring-born colts had reached this weight in the winter (May and June, before day length had increased) but did not exhibit a significant testosterone response until the spring at a mean weight of 352 kg (327-403 kg). It is proposed that colts must achieve a threshold body weight concurrently with stimulatory photoperiod for onset of puberty to occur.     

Children with isolated growth hormone deficiency: Empty sella versus normal sella

BACKGROUND:

Empty sella (ES) may be associated with variable clinical conditions ranging from the occasional discovery of a clinically asymptomatic pouch within the sella turcica to severe intracranial hypertension and rhinorrhea. The need for replacement hormone therapy in ES, as in other syndromes that may cause hypopituitarism, must be assessed for every single hormone, including growth hormone (GH).

AIM:

To determine whether or not the presence of ES could allow some changes in the GH responses of the isolated growth hormone deficiency (GHD) patients.

MATERIALS AND METHODS:

We included a cohort of 59 short stature children and adolescents with isolated GHD. According to computed tomography finding, they were classified into 2 groups: Group 1 included 40 children with normal sella and 19 children with ES in Group 2. All patients received recombinant human growth hormone (rhGH) with a standard dose of 20 IU/m²/week.

RESULTS:

The baseline results were not significantly different for all variables except weight standard deviation was smaller with statistical significant difference (P = 0.02). We identified no significant differences when comparing both groups, except for height standard deviation (HTSD) after the first year of therapy which revealed significant difference in favor of group 1. When comparing pre- and the two post-treatments HTSD results of the studied cases, all showed significant changes after GH therapy. The results of related variables pre-and post-treatment in both the groups showed significant improvement in all variables of the two groups of the study.

CONCLUSION:

Our study showed a similar stature outcome in the two treatment groups.     

Effect of Testosterone on Insulin Sensitivity in Men with Idiopathic Hypogonadotropic Hypogonadism

ObjectiveTo assess the presence of insulin resistance (IR) among a homogeneous cohort of male patients with idiopathic hypogonadotropic hypogonadism (IHH) and to investigate the effects of testosterone therapy on IR in this specific group.MethodsTwenty-four male patients with untreated IHH and 20 age-, sex-, and weight-matched eugonadal healthy control subjects were recruited for the study. Plasma glucose, plasma insulin, total and free testosterone, follicle-stimulating hormone, luteinizing hormone, estradiol, and sex hormone-binding globulin levels were measured in fasting blood samples, and biochemical and hormonal analyses were performed for all study participants. IR was calculated by the homeostasis model assessment of insulin resistance (HOMA-IR) formula and the quantitative insulin sensitivity check index (QUICKI). Body mass index was calculated by weighing and measuring the heights of all study participants at the beginning of the investigation. Body fat mass and body lean mass were calculated as percentages of body weight by bioelectrical impedance analysis of body composition. Sustanon 250 (a combination of 4 testosterones) was administered intramuscularly once every 3 weeks for 6 months to male patients with IHH after a basal anthropometric, biochemical, and hormonal evaluation. The response to therapy was monitored by regular clinical examinations and serum testosterone measurements. After 6 months of testosterone treatment, the entire anthropometric, biochemical, and hormonal evaluation was repeated 14 days after the last injection of testosterone.ResultsBefore treatment, male patients with IHH had higher fasting plasma glucose concentrations, higher fasting plasma insulin levels, a higher HOMA-IR score, and a lower QUICKI when compared with the control group. After testosterone treatment in the patient group, the HOMA-IR score decreased dramatically to the level in the control group. The high body fat mass of the male patients with IHH was reduced significantly after testosterone treatment, concomitant with significant increases in body mass index and body lean mass.ConclusionInsulin sensitivity improves and body fat mass decreases with long-term testosterone replacement therapy. (Endocr Pract. 2007;13:629-635)     

Hypothalamic hypogonadism: induction of ovulation and pregnancy by subcutaneous pulsatile injections of gonadotrophin-releasing hormone

5 female patients with isolated hypothalamic hypogonadism were given subcutaneous pulses of gonadotrophin-releasing hormone (GnRH), 2.5-15 micrograms every 90 min, for 2-6 months by means of an automated pump. This treatment produced an increase in serum LH, FSH, and estradiol levels in 4 patients, all of whom became pregnant. The estradiol levels failed to rise in 1 patient, in spite of an adequate LH and FSH response, and a subsequent biopsy showed evidence of primary ovarian failure in addition to the hypothalamic deficit. We conclude that subcutaneous pulsatile GnRH administration is a simple, safe, and relatively inexpensive way to induce ovulation in patients with hypothalamic hypogonadism.