Hormones and the Bone Marrow: Panhypopituitarism and Pancytopenia in a Man with a Pituitary Adenoma

In rare cases, pancytopenia results from hormonal deficiencies that arise in the setting of panhypopituitarism. Here we describe the unusual case of a 60-year-old man who presented with progressive fatigue and polyuria, and whose laboratory workup revealed a deficiency of the five hormones associated with the action of the anterior pituitary (thyroid hormone, testosterone, cortisol, prolactin, and insulin-like growth factor-1). Imaging of the pituitary demonstrated a cystic mass consistent with a pituitary adenoma replacing much of the normal pituitary tissue. His symptoms and hematologic abnormalities rapidly resolved with prednisone and levothyroxine supplementation. While the majority of reported cases of panhypopituitarism with bone marrow suppression are the result of peripartum sepsis or hemorrhage leading to pituitary gland necrosis (Sheehan’s syndrome), it is also important to consider the diagnosis of hypopituitarism in patients with hypothyroidism, low cortisol levels, and pancytopenia. The causal relationship between pancytopenia and panhypopituitarism is not well understood, though it does reinforce the important influence of these endocrine hormones on the health of the bone marrow.KEY WORDS: pancytopenia, panhypopituitarism, hypopituitarism, Sheehan’s syndrome, pituitary adenoma     

Hematological response of pancytopenia to glucocorticoids in patients with Sheehan’s syndrome

Sheehan??s syndrome presents with panhypopituitarism after childbirth, usually preceded by post partum hemorrhage. Hematological abnormalities like pancytopenia with hypocellular marrow in these patients are reported rarely. Though multiple hormone deficiencies may contribute to Pancytopenia in Sheehan??s syndrome, complete recovery is observed after achieving eucortisolemic and euthyroid state. The predominant role of thyroxine or glucocorticoids in reversing pancytopenia in these patients has not been studied. We present the clinical, hormonal, hematological course and response to glucocorticoids in a patient of Sheehan??s syndrome presenting with pancytopenia. Complete recovery of pancytopenia was observed after achieving eucortisolemic state thus concluding that gulcocorticoid replacement is sufficient to reverse pancytopenia in these patients.     

Remarkable response to rituximab in a patient with atypical CD20<Superscript>++</Superscript> mantle cell lymphoma of the bone marrow leading to severe pancytopenia

Rituximab, a chimeric monoclonal antibody which binds to the CD20 antigen, has been reported in several studies to induce remissions in low- and high-grade non-Hodgkins lymphoma without causing myelosuppression. We report here a case of a 68-year-old female patient with an atypical mantle cell lymphoma infiltrating only the bone marrow without leukemic involvement or any other nodal or extranodal manifestations. Progressive severe pancytopenia due to the diffuse bone marrow infiltration led to life-threatening infections following oral chlorambucil treatment. No response to chlorambucil was noted. The patient attained a complete remission after salvage therapy with four weekly infusions of single-agent rituximab at a standard dose of 375 mg/m². Thus, anti-CD20 antibody may be the treatment of choice for patients with CD20⁺ B-non-Hodgkins lymphoma who cannot tolerate chemotherapy due to high risk of infectious complications as a result of severe pancytopenia.     

Expert opinion on pituitary complications in immunotherapy

Hypophysitis is a frequent toxic endocrine side-effect of immunotherapy. Prevalence is higher with anti-CTLA-4 antibodies (4–20%) or in association with PD-1 inhibitors (8%). Diagnosis is presumptive, based on poorly specific clinical symptoms (usually, headache and asthenia) and/or hyponatremia and/or at least one pituitary deficit and/or abnormal imaging. Visual disorder or polyuropolydipsic syndrome are exceptional. In decreasing order of frequency, deficits are thyrotropic (86–100%), gonadotropic (85–100%) or corticotropic (50–73%); somatotropin deficit or abnormal prolactin level are rarer. Pituitary MRI in acute phase shows variable moderate increase in pituitary volume, ruling out differential diagnoses, especially pituitary metastasis. Treatment of corticotropin deficiency requires systematic emergency replacement therapy, with the usual modalities, while treatment of other deficits depends on clinical status and progression. Thyrotropin and gonadotropin deficits usually recover, but corticotropin deficiency persists over the long term, requiring education and specialized endocrinologic follow-up. Onset of hypophysitis does not contraindicate continuation of immunotherapy and does not usually require high dose synthetic glucocorticoids.Recommendations

• •R1: Diagnosis of hypophysis under immunotherapy is based on suggestive clinical symptoms (usually, headache or asthenia) and/or hyponatremia and/or at least one pituitary deficit and/or abnormal imaging.
• •R2: Surgical biopsy for histologic confirmation of hypophysitis under immunotherapy is not indicated if there is no evidence of other pituitary pathology such as metastasis.
• •R3: In suspected hypophysitis:
  • ∘blood ionogram should be performed;
  • ∘hormonal work-up should include:
    • –T4L (and TSH, given the risk of thyroid involvement under immunotherapy),
    • –cortisolemia and ACTH (given reports of rare cases of primary adrenal insufficiency) at 8 am (except in acute cases; see R6) in the absence of glucocorticoid drug treatment, with dynamic testing according to findings,
    • –LH, FSH and estradiol in non-menopausal females without oral contraception in case of menstrual disorder, or FSH in menopausal females; LH, FSH and total testosterone in males,
    • –blood prolactin.

All these results are to be interpreted in the light of the context (cancer treatment, polymedication) and compared with the initial hormonal work-up (cf. R10).

• ∘Polyuropolydipsic syndrome should systematically be screened for clinically (given reports of rare cases of diabetes insipidus).
• ∘Screening for somatotropin deficiency is unnecessary.
• ∘MRI should be performed, centered on the pituitary gland, with gadolinium injection, ideally in acute phase, to confirm diagnosis and rule out differential diagnoses (notably, pituitary metastasis). Normal MRI does not rule out diagnosis.

• •R4: If MRI suggests hypophysitis but with no pituitary deficit, close biological monitoring of 8-am cortisolemia should be initiated, weekly for 1 month then as in usual follow-up (cf. R11). Dynamic corticotropic function test may be performed, depending on 8-am cortisolemia and clinical status.
• •R5: In proven hypophysitis, high-dose glucocorticoid drugs are not systematically recommended, but may be used symptomatically for severe headache not responding to usual analgesia and/or for visual disorder.
• •R6: In suspected acute corticotropin insufficiency under immunotherapy, emergency plasma cortisol assay should be performed regardless the time of day. Intravenous, intramuscular or subcutaneous 100 mg hydrocortisone hemisuccinate injection should be followed by 24 hours’ continuous infusion of 100 mg hydrocortisone hemisuccinate, as in acute corticotropin insufficiency unrelated to immunotherapy, without awaiting cortisol and ACTH assay results. When clinical and biological symptoms begin to improve, oral hydrocortisone relay should be initiated at 60 mg per 24 hr divided in 3 doses, then progressively reduced to the replacement dose.
• •R7: In chronic corticotropin insufficiency under immunotherapy, daily hydrocortisone dose is 15–20 mg/day in 2–3 doses per day, adapted to clinical parameters. The patient should be followed up by an endocrinologist for therapeutic education. How to adapt hydrocortisone to acute events should also be explained to the patient and the oncologist.
• •R8:
  • ∘in case of thyrotropin deficiency, levothyroxine therapy should be considered on a case-by-case basis, according to severity, clinical tolerance and/or clinical and biological progression (free T4) assessed on the evaluation at 1 month,
  • ∘in case of gonadotropin deficiency, estroprogestative replacement in under-50 year-old females or androgen replacement in males is considered according to progression during the first 3 months’ monitoring if there are no oncologic contraindications,
  • ∘diabetes insipidus is to be treated systematically,
  • ∘in this oncologic context, no replacement therapy for somatotropin deficiency is indicated (cf. R2).
• •R9: Hypophysitis does not contraindicate continuation of immunotherapy, which may, however, be interrupted during the acute phase of symptomatic hypophysitis. Onset of hypophysitis secondary to administration of one immunotherapy molecule (anti-CTLA-4, anti-PD-1 or anti-PD-L1) does not contraindicate switching to another. History of pituitary pathology does not contraindicate immunotherapy; replacement therapy may need to be adapted.
• •R10: We recommend systematic blood ionogram, and assays of 8-am cortisol (in the absence of glucocorticoid drug treatment); TSH and T4L; LH, FSH and total testosterone in males, or LH, FSH and estradiol in non-menopausal females without oral contraception in case of menstrual disorder, or FSH in menopausal females ahead of first immunotherapy injection. Pituitary MRI ahead of immunotherapy is not recommended.
• •R11: We recommend taking an ionogram, with clinical and hormonal monitoring (8-am cortisol in the absence of glucocorticoid drug treatment, TSH, T4L, total testosterone in males and interview on menstrual disorder in non-menopausal females) at each immunotherapy course for the first 6 months. If the patient is asymptomatic and hormonal work-up is normal, monitoring should then be done every 2 months for 6 months and only in case of suggestive symptoms after 12 months. Systematic pituitary MRI during follow-up is not recommended.
• •R12: In patients developing hypophysitis, clinical and hormonal assessment (pituitary assessment to screen for new deficits and adapt treatment) should be performed at each immunotherapy course for 6 months, then in specialist consultation every 3 months for 6 months, then twice yearly. Given the possibility of hormonal functional recovery, gonadotropin and thyrotropin axis replacement therapy may, depending on clinical status, be withdrawn under specialized monitoring. Pituitary MRI should be repeated once at 3 months to rule out differential diagnosis of pituitary metastasis and assess progression of pituitary inflammation.

     

Gene expression signature for early prediction of late occurring pancytopenia in irradiated baboons

Based on gene expression changes measured in the peripheral blood within the first 2 days after irradiation, we predicted a pancytopenia in a baboon model. Eighteen baboons were irradiated with 2.5 or 5 Gy. According to changes in blood cell counts, the surviving baboons (n = 17) exhibited a hematological acute radiation syndrome (HARS) either with or without a pancytopenia. We used a two stage study design where stage I was a whole genome screen (microarrays) for mRNA combined with a qRT-PCR platform for simultaneous detection of 667 miRNAs using a part of the samples. Candidate mRNAs and miRNAs differentially upregulated or downregulated (>2-fold, p < 0.05) during the first 2 days after irradiation were chosen for validation in stage II using the remaining samples and using throughout more sensitive qRT-PCR. We detected about twice as many upregulated (mean 2128) than downregulated genes (mean 789) in baboons developing an HARS either with or without a pancytopenia. From 51 candidate mRNAs altogether, 11 mRNAs were validated using qRT-PCR. These mRNAs showed only significant differences between HARS groups and H0, but not between HARS groups with and without pancytopenia. Six miRNA species (e.g., miR-574-3p, p = 0.009, ROC = 0.94) revealed significant gene expression differences between HARS groups with and without pancytopenia and are known to sensitize irradiated cells. Hence, in particular, the newly identified miRNA species for prediction of pancytopenia will support the medical management decision making.     

Effect of long-term treatment with recombinant human growth hormone on erythropoietin secretion in an anemic patient with panhypopituitarism

We studied the effect of treatment with recombinant human GH in an anemic patient with panhypopituitarism in which hemoglobin (Hb) concentration remained as low as 11.0 g/dl in spite of appropriate replacement with thyroid and adrenocortical hormones. Recombinant human GH was subcutaneously and constantly infused for 12 months using a portable syringe pump at a rate of 0.25 U/kg/week. After the treatment with human GH plasma erythropoietin (EPO) levels increased from 12.2 to 25.1 mIU/ml, with a concomitant increase of Hb concentration to 13.6 g/dl. When the administration of human GH was interrupted, both plasma EPO levels and Hb concentrations decreased. There was a close correlation between plasma GH and EPO levels before and during the human GH administration (y=2.444x+1 3.423, r=0.641, p<0.05). Plasma GH levels were well correlated with Hb concentrations before and during human GH administration (y=0.529x+11.313, r=0.690, p<0.01). Plasma IGF4 levels were also correlated with Hb concentrations (y=0.007x+10.874, r=0.832, p<0.001), but not with plasma EPO levels. These findings suggest that GH treatment may be useful in anemic patients with panhypopituitarism.     

Acute sterile meningitis as a primary manifestation of pituitary apoplexy

Pituitary apoplexy is a rare and underdiagnosed clinical syndrome. It results from hemorrhagic infarction of the pituitary gland. In its classical form it is characterized by acute headache, ophthalmoplegia, visual loss and pituitary insufficiency. Meningeal irritation signs, clinically indistinguishable from infectious meningitis, are considered rare and have not been reported as presenting signs. We report a 53-yr-old man who was admitted to hospital following acute headache, fever, neck stiffness and paresis of the left oculomotor and abducent nerves. A lumbar puncture revealed an increased number of polymorphs but with a sterile cerebral spinal fluid. Magnetic resonance imaging (MRI) showed an intrasellar mass with central necrosis in an enlarged sella. Endocrinological evaluation demonstrated insufficient thyroid, adrenocortical, and gonadal function. Necrosis within a chromophobe adenoma was found upon surgical decompression of the sella. After surgery anterior panhypopituitarism did not recover, while ophthalmoplegia subsided. The patient is now in good health under appropriate hormonal replacement therapy.     

Correction of cortisol overreplacement ameliorates morbidities in patients with hypopituitarism: a pilot study

CONTEXT: Hyporituitarism in adults is known to be associated with deleterious effects on body composition, lipid profile and quality of life (QoL). This was attributed to GH deficiency. The potential role of glucocorticoid overreplacement had never been investigated. OBJECTIVE: To investigate whether reduction in glucocorticoid replacement dose to more physiological one could ameliorate the "AO-GHD"-attributed symptomatology in patients with hypopituitarism. Design Eleven patients with panhypopituitarism taking 20-30 mg/day of hydrocortisone, but on no GH replacement were switched to 10-15 mg of hydrocortisone daily. Both basally and 6-12 months later, their body mass index, body composition by dual-energy X-ray absorptiometry, lipid profile, and the score of quality of life, QOL-AGHDA were measured. RESULTS: Within 6-12 months of lower hydrocortisone dose, subjects lost an average of 7.1 kg of total body fat and 4.1 kg of abdominal fat. No changes were seen in lean body mass, bone mineral content and HOMA-IR. Plasma total cholesterol and triglyceride concentrations decreased significantly (< 0.05) and the QoL improved (P = 0.018). CONCLUSIONS: Our pilot study suggests that decreasing the glucocorticoid replacement dose to approximately 15 mg/day is beneficial in terms of patients' body composition, lipid profile and quality of life.     

Hypothalamitis: a diagnostic and therapeutic challenge

To report an unusual case of biopsy-proven autoimmune hypophysitis with predominant hypothalamic involvement associated with empty sella, panhypopituitarism, visual disturbances and antipituitary antibodies positivity. We present the history, physical findings, hormonal assay results, imaging, surgical findings and pathology at presentation, together with a 2-year follow-up. A literature review on the hypothalamic involvement of autoimmune hypophysitis with empty sella was performed. A 48-year-old woman presented with polyuria, polydipsia, asthenia, diarrhea and vomiting. The magnetic resonance imaging (MRI) revealed a clear suprasellar (hypothalamic) mass, while the pituitary gland appeared atrophic. Hormonal testing showed panhypopituitarism and hyperprolactinemia; visual field examination was normal. Pituitary serum antibodies were positive. Two months later an MRI documented a mild increase of the lesion. The patient underwent biopsy of the lesion via a transsphenoidal approach. Histological diagnosis was lymphocytic “hypothalamitis”. Despite 6 months of corticosteroid therapy, the patient developed bitemporal hemianopia and blurred vision, without radiological evidence of chiasm compression, suggesting autoimmune optic neuritis with uveitis. Immunosuppressive treatment with azathioprine was then instituted. Two months later, an MRI documented a striking reduction of the hypothalamic lesion and visual field examination showed a significant improvement. The lesion is stable at the 2-year follow-up. For the first time we demonstrated that “hypothalamitis” might be the possible evolution of an autoimmune hypophysitis, resulting in pituitary atrophy, secondary empty sella and panhypopituitarism. Although steroid treatment is advisable as a first line therapy, immunosuppressive therapy with azathioprine might be necessary to achieve disease control.     

Hormones and the Aging Process

For more than a century, it has been suggested that failure of the secretions of the ductless glands leads to aging. Replacement of these hormones has been suggested as a method of slowing the aging process. Clearly, modern research has demonstrated that the concept of a "hormonal fountain of youth" is predominantly mythology. The best evidence for hormonal replacement is vitamin D and estrogen replacement to prevent hip fractures. Other than that, treatment should be limited to hormone replacement in persons who have endocrine disease.     

Hemophagocytic syndrome in ileum-origin B-cell lymphoma

A 56 year-old-man was admitted due to upper abdominal tumor and was diagnosed as having stage IVb diffuse B-cell malignant lymphoma that originally developed in the terminal ileum. The first and the second administrations of CHOP (cyclophosphamide, 750mg/m²; adriamycin, 50mg/m²; vincristine, 1.4mg/m²; and prednisolone, 100mg/day) therapy were effective; however, the third course of therapy was postponed because of an episode of massive hematochezia. After this episode, lymph nodes began to enlarge and progressive pancytopenia occurred. Bone marrow smear showed the proliferation of reactive histiocytic cells which phagocytized red blood cells, white blood cells, and platelets. B-cell lymphoma-associated hemophagocytic syndrome (B-LAHS) was diagnosed. This case is extremely rare because: (1) LAHS occurred in an ileum-origin B-cell lymphoma, and (2) LAHS developed during an interval after chemotherapy.     

Hormonal and reproductive risk factors for development of systemic lupus erythematosus: Results of a population‐based,case–control study

Objective

Estrogen and prolactin may accelerate the progression of murine systemic lupus erythematosus (SLE). In humans, 85% of lupus patients are women, which also suggests the importance of hormonal factors in disease pathogenesis. The purpose of this study was to examine hormonal and reproductive risk factors for lupus among women.

Methods

This population‐based, case–control study included 240 female SLE patients diagnosed between January 1, 1995 and July 31, 1999 who fulfilled the American College of Rheumatology classification criteria. Female controls (n = 321) were identified through driver's license records. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) as measures of association, adjusting for age, state, race, and education. Analyses were limited to exposures before diagnosis.

Results

Breast‐feeding was associated with a decreased risk of developing SLE (OR 0.6, 95% CI 0.4–0.9), with a statistically significant trend for number of babies breast‐fed and total weeks of breast‐feeding. There were no associations with number of pregnancies or live births. Natural menopause occurred earlier in women with subsequent development of SLE compared with controls (P < 0.001). There was little association between SLE and current use or duration of use of hormone replacement therapy or oral contraceptives, and no association with previous use of fertility drugs.

Conclusion

We found little evidence that estrogen‐ or prolactin‐related exposures are associated with an increased risk of lupus. The reduced risk observed among women who had breast‐fed one or more babies should be examined in other studies. Early natural menopause, rather than decreasing risk of SLE because of reduced estrogen exposure, may be a marker of susceptibility to development of SLE.

     

Effects of verapamil on exocrine pancreatic secretion in man

Calcium ions are thought to mediate hormonal and cholinergic stimulation of exocrine pancreatic secretion. In order to further eludicate the role of calcium ions in stimulus-secretion coupling of the pancreas, the effect of the calcium antagonist verapamil, which inhibits transmembrane calcium influx, was studied on pancreatic secretion in 35 healthy male volunteers. Every subject had two stimulation periods of 2 hr each with a 3-hr period between the two. Pancreatic secretion was stimulated by cholecystokinin in 12 subjects, by secretin in 14 subjects, and by sham feeding in 6 subjects. Three subjects were studied without any secretory stimulus. Verapamil as an intravenous bolus of 150 g/kg followed by an intravenous infusion of 150 g/kg/hr or saline were given during the two 2-hr stimulation periods in a randomized order. The pancreatic secretory responses to stimulation by cholecystokinin, secretin, or sham feeding, as well as the basal pancreatic secretion without a secretory stimulus were left unaffected by verapamil when compared to the saline control. The results, therefore, call into question the hypothesis that transmembrane calcium influx is a major mediator of pancreatic secretion in response to hormonal or cholinergic stimulation in man.The authors were supported by a grant of the Deutsche Forschungsgemeinschaft (DFG-Ni 224/1-1).     

An anatomical study of a new method for enlargement of narrowed aortic annulus: Intra-arterial aorto-infundibuloplasty

Summary A new procedure intraarterial aortoinfundibuloplasty for the narrowed aortic annulus is described. Aortic valve replacement is performed through an aorto-pulmonary and infundibular septal incision which is eventually enlarged by a single patch, i.e., a two-dimensional patch instead of a three-dimensional patch as in Konno's procedure.An anatomical study showed that a prosthetic valve three sizes larger than the natural annular diameter could be implanted and the natural annular diameter was increased by as much as 42%.     

A problem of control of treatment in a boy with salt-losing congenital adrenal hyperplasia (21-hydroxylation defect)

Inadequate mineralocorticoid replacement is shown to have been the cause of elevated levels of plasma ACTH and 17-hydroxyprogesterone and of urinary steroids in a boy with salt-losing congenital adrenal hyperplasia who was receiving more than adequate glucocorticoid replacement.     

Hodgkin lymphoma in temporal association with growth hormone replacement

The association between growth hormone (GH) replacement and malignancy has long been debated. We report a case of Hodgkin lymphoma that developed in temporal association with the initiation of GH replacement in a 57-year-old woman with panhypopituitarism secondary to a non-secretory pituitary macroadenoma. Treatment of her pituitary tumor included transphenoidal surgery, external beam radiation, Bromocriptine and Cabergaline therapy. In addition to replacement steroid, thyroid and sex hormones, she insisted on GH replacement. Approximately 2 years after GH initiation, the diagnosis of Hodgkin lymphoma was made. Although the exact contribution of GH to the development of Hodgkin disease in our patient is unclear and a causal effect cannot be concluded, the temporal association is suggestive, and warrants reporting as part of ongoing surveillance for potential complications of GH replacement.     

Reproductive and endocrine gonadal capacity in patients treated with COPP chemotherapy for Hodgkin's disease

Summary Testicular and ovarian functions were assessed in 33 patients with Hodgkin's disease 1 to 17 years after cessation of COPP chemotherapy with cyclophosphamide, vincristine, procarbazine, prednisone. Diagnostic procedures consisted of hormone measurements, interviews, and semen analyses. In women serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), 17-estradiol, progesterone, prolactin, and in men FSH, LH, 17-estradiol, testosterone, and prolactin were determined. Semen analyses were performed in all men. Information concerning pregnancies, pregnancy outcome, future fertility wishes, sexual functions, menstrual pattern, and incidence of premature menopausal symptoms was ascertained by interview and questionnaire. Nineteen of 19 (100%) men showed elevated serum FSH levels between 715 and 1910 (median 1095) ng/ml and azoospermia, 1 to 11 years afters therapy. Serum levels of testosterone were within normal limits in 18/19 (95%) of the men, and LH values were normal in all men. Permanent ovarian failure occurred in 8/14 (57%) women, causing infertility and premature menopausal symptoms. The incidence of ovarian failure in women over 24 years was 86% (6/7) versus 28% (2/7) in those under 24 years at the time of treatment. In women receiving estrogen replacement, incidence and severity of these symptoms were significantly reduced. Of 14 women 3(21%) became pregnant and delivered 5 healthy children after treatment. Our results suggest irreversible sterility and normal Leydig cell function after COPP chemotherapy in all men. Druginduced ovarian failure was age-related and caused premature menopausal symptoms, detracting from the quality of the patient's life. To reduce premature menopausal symptoms and to prevent adverse cardiovascular and metabolic late sequelae, hormonal replacement is indicated. Pregnancies ending in normal live births can be achieved after COPP chemotherapy in young women. In both men and women, serum FSH and LH levels proved to be feasible markers to determine degree and duration of endocrine and reproductive gonadal injury after chemotherapy.Supported in part by a grant from Deutsche Krebshilfe (M16/86 He 3)     

Recovery of HPA Axis Function After Successful Gonadotropin-Induced Pregnancy and Delivery in a Woman With Panhypopituitarism: Case Report and Review

Hypopituitarism is defined as the partial or complete defect of anterior pituitary hormone secretion. Patients with hypopituitarism usually need life-long hormone replacement therapy. However, in this case, we report a patient with panhypopituitarism whose hypothalamus–pituitary–adrenal (HPA) axis function was completely recovered after pregnancy and delivery.In this case study, we reported the case management and conducted a review of literature to identify the possible mechanism of pituitary function recovery.The patient who suffered from secondary amenorrhea was found a nonfunctioning pituitary macroadenoma, and the hormone test showed serum cortisol, FT3, FT4, thyrotropic hormone, and prolactin were at normal range. After surgical removal of the tumor which invasion in the sellar region, the patient had panhypopituitarism confirmed by the routine hormone test. Though spontaneous pregnancy is impossible in female patients with panhypopituitarism, the patient was restored fertility by the help of artificial reproductive techniques. After the confirmation of the pregnancy, levothyroixine was increased to 75 μg daily and readjusted to 150 μg daily before delivery according to the monthly measurement thyroid function. Hydrocortisone 10 mg daily replaced cortisone acetate; the dose was increased according to the symptoms of morning sickness. A single stress dose of hydrocortisone (200 mg) was used before elective cesarean delivery and was tapered to the dose of 10 mg per day in 1 week. Levothyroixine was reduced to 75 μg daily after delivery. During follow-up, her hypothalamus–pituitary–adrenal (HPA) axis function was completely recovered. The peak serum cotisol level could increase to 19.08 μg/dL by insulin-induced hypoglycemia. However, growth hormone remained unresponsive to the insulin-tolerance test, and thyroid hormone still needed exogenous supplementation.Hormone replacement therapy needed closely followed by endocrinologist and multidisciplinary cooperation during the pregnancy of patients with hypopituitarism. This case indicates that the pituitary function may partially recover after pregnancy in panhypopituitarism patients.     

Adipose tissue development “in Utero”

Summary Some metabolic and hormonal variables, thought to affect adipose tissue development in utero were studied in a group of 50 presumably healthy mothers and in their full-term infants. No sex-related differences were observed at birth in skinfold thickness, body fat mass, fat cell volume or fat cell number. Body fat mass in newborns was significantly correlated to fat cell size (r=0.75; p< 0.001), but not to fat cell number. Weight gain during pregnancy but not prepregnancy weight was correlated to fat cell volume in the newborn (r=0.67; p<0.001) and to body fat mass (r=0.66; p< 0.001). Maternal placental lactogen levels correlated to decreased glucose tolerance in the mothers (r= 0.62; p<0.001), as well as to body fat mass (r= 0.61; p<0.001) and fat cell size (r=0.58; p< 0.001) in newborns. Neonatal plasma insulin levels in addition correlated with body fat mass (r=0.39; p< 0.05) and fat cell weight (r=0.69; p<0.001) of the neonate. Placental NEFA transfer could be demonstrated, but there was no correlation between maternal plasma NEFA levels and neonatal body fat mass or fat cell weight. Similarly, maternal insulin and growth hormone levels were not correlated with neonatal body fat mass or with fat cell size or number. Thus the nutritional and hormonal factors considered do not appear to be involved in fat cell multiplication. During intrauterine life, in full-term infants of presumably healthy mothers, fat mass expansion seems to occur almost exclusively by means of fat cell hypertrophy.     

Congenital hypopituitarism in a 48-year old adult. Natural course, hormonal study and MRI evidence

A case of Congenital Hypopituitarism (CH) in an untreated 48 yr-old-man is reported. The hormonal studies demonstrated a panhypopituitarism and MR imaging revealed absence of pituitary stalk, small anterior pituitary remnant on the sella floor and ectopic neurohypophysis at the tuber cinereum. The pattern of hormonal responsiveness suggests that CH encompasses findings typical of primary anterior pituitary disease and those of hypothalamic dysfunction.