Medical management after pituitary surgery

Although the majority of patients with pituitary tumor, undergoing transsphenoidal microsurgery, have a low incidence of hormonal deficiency after surgery, the endocrinological evaluations should be carefully done before and after surgery. Glucocorticoid replacement is necessary in patients with Cushing's disease during and after surgery as well as those with adrenal insufficiency. Repeated CRF test is useful to assess the secondary adrenal insufficiency of Cushing's disease after surgery. Patients with impaired secretion of both ACTH and TSH should receive glucocorticoid replacement before thyroid hormone replacement in order to avoid adrenal crisis. A combination of CRF, GRF, TRH and GnRH is a safer and more reliable test to evaluate pituitary function than the conventional triple test consisting of insulin, TRH and GnRH, especially in patients predicted to have pituitary-adrenal insufficiency. Diabetes insipidus(DI), immediately after pituitary surgery, should be treated with subcutaneous injection of Pitressin. Even if patients seem to have recovered from DI several days after surgery, they must be monitored closely because of the incidence of triphasic DI. Less attention has been given to replacement for GH deficiency in adults. Recent reports revealed that GH replacement in adults with GH deficiency decreases visceral fat tissue and increases plasma calcium, phosphorus, osteocalcin and procollagen III levels. GH replacement will become more popular even in adults. Many options and technological advantages in the diagnosis and treatment of pituitary tumors have developed in a decade. In the near future, post-operative patients with pituitary tumors must be cared for in view of the "quality of life".     

Isolated ACTH deficiency

The isolated ACTH deficiency is a scarcely diagnosed disease of heterogeneous nature. Two patients with isolated deficiency of ACTH in whom the initial diagnosis was of primary suprarrenal failure are reported. In the first case this diagnosis was performed after hospital admission for deterioration of the level of consciousness and the development of an acute suprarrenal crisis in the course of nosocomial pneumonia. In the second case the clinical manifestations began as weakness, anorexia, weight loss and lymphocytosis with eosinophilia. In both patients an increase in the thyrotropic hormone was detected leading to suspicion of the existence of associated primary hypothyroidism. Finally, several studies were carried out (basal measurements of cortisol and ACTH, stimulation with continual perfusion of ACTH, insulinic hypoglycemia, global study of adenohypophysary function, ACTH CRF release factor test, computerized tomography of the pituitary region) in both patients leading to the definitive diagnosis of isolated ACTH deficiency of idiopathic cause of possible pituitary origin without the existence of other associated hormonal deficiencies.     

Incidental pituitary macroadenoma: a population-based study

Epidemiologic analysis of incidental macroadenoma is limited to autopsy studies and case series. There are no published data about prevalence of incidental pituitary macroadenoma in living patients. The objective of this study was to determine the prevalence of incidental pituitary macroadenoma. It was designed as an observational study of cranial computed tomography reports. An urban department of veterans affairs medical center was used for the setting. The subject group consisted of 3,550 consecutive patients at the Cleveland Department of Veterans Affairs Medical Center from January 1993 to January 1996. Patients with known or suspected pituitary or parasellar disease were excluded. Cranial computed tomography reports were reviewed. Original films and medical charts of all patients with pituitary macroadenoma were reviewed. Seven patients with incidentally discovered pituitary macroadenoma that ranged from 1 cm to 2.5 cm were found; prevalence was 0.20% (95% confidence interval 0.05, 0.35%). Evidence of partial hypopituitarism was found in most patients. All patients had normal visual fields at initial examination despite the size of the tumor, but 1 of 4 had a field cut demonstrated by Goldmann perimetry. These data confirm that, although the prevalence of incidental pituitary macroadenoma is low, screening identified patients to detect deficiency of corticotropin, thyroid-stimulating hormone, and gonadotropins and to detect visual field defects is important.     

Radiation injury of the lung following postoperative radiotherapy of breast cancer using a single large portal technique--CT study

Magnetic resonance imaging demonstrated coexistent central nervous system abnormalities in 30 of 40 patients with optic nerve hypoplasia. Based on their associated neuroradiological findings, these patients were placed into one of five categories: group 1, isolated optic nerve hypoplasia; group 2, absence of the septum pellucidum; group 3, posterior pituitary ectopia; group 4, hemispheric migration anomalies; and group 5, intrauterine/perinatal hemispheric injury. Posterior pituitary ectopia (group 3) and cerebral hemispheric abnormalities (groups 4 and 5) were found to be highly predictive of pituitary hormone deficiency and neurodevelopmental deficits, respectively. Isolated absence of the septum pellucidum (group 2) was associated with normal neurodevelopmental and endocrinologic function. Thinning or agenesis of the corpus callosum was predictive of neurodevelopmental problems only by virtue of its frequent association with cerebral hemispheric abnormalities. Magnetic resonance imaging can now be used to provide specific prognostic information regarding the likelihood of neurodevelopmental deficits and pituitary hormone deficiency in infants with optic nerve hypoplasia. The prevailing notion of septo-optic dysplasia as a distinct nosologic entity should be reconsidered.     

Growth hormone deficiency and its treatment in adults

Deficiency of growth hormone produced in the pituitary is manifested not only in children by impaired growth but also in adults. It is encountered most frequently in adults after surgery or irradiation in the hypothalamo-pituitary area, less frequently in idiopathic disorders of growth hormone production and secretion, either isolated or in conjunction with other trophic pituitary hormones. The diagnosis of growth hormone deficiency must be assessed by dynamic stimulation tests: most frequently the insulin stimulation test is used. Growth hormone deficiency in adult age is manifested by various non-specific symptoms which resemble symptoms (manifestations) of ageing: increase of adipose tissue, deterioration of lipid metabolism, osteopenia, impaired cardiac output and others; the symptoms recede partly if growth hormone is administered for a prolonged period. Clinical trials which are under way should define not only suitable indications but also ways of administration of this expensive treatment.     

Combined deficiency of thyroid stimulating hormone and growth hormone in a diabetic patient with Hashimoto thyroiditis

We report the case of a 36-year-old female patient with insulin dependent diabetes who developed hypothyroidism of pituitary origin after giving birth. She had low levels of free T4 and TSH with no response to i.v. TRH. Antimicrosome antibodies were increased (1/25000), suggesting Hashimoto's thyroiditis. The other hormones were normal except for a low level of growth hormone and insulin growth factor 1. There were no antibodies against the pituitary. MRI of the pituitary was normal. We suspect a vascular origin for this partial pituitary deficiency.     

Application of genetic markers to the identification of recrudescent Plasmodium falciparum infections on the northwestern border of Thailand

PATIENTS AND METHODS: The role of cerebral magnetic resonance imaging (MRI) in the diagnosis of growth hormone (GH) deficiency in children has been studied in 100 children. The diagnosis of GH deficiency was assessed at a mean age of 6.7 +/- 4.1 years: morphological abnormalities of the hypothalamic-pituitary (HP) region have been studied in three different groups: in the first group (70 cases), the neurohypophysis was present and normally located; in the second group (ten cases) it was missing; in the third group (20 cases) the neurohypophysis was ectopic (truncated stalk syndrome with ectopic neurohypophysis, small antehypophysis, thin or non-visualized stalk). RESULTS: In the majority of cases, children presenting with only one morphological abnormality of the HP region (ectopic neurohypophysis or small antehypophysis or non-visualized or thin stalk) had an isolated GH deficiency. When multiple morphological abnormalities were present, anterior pituitary deficiency was multiple in more than half the cases. Cerebral midline anomalies (above all Chiari I malformation and basipharyngeal canal) had been observed in 20% of the children presenting with GH deficiency. In the majority of cases (95%), these anomalies were associated with one or more abnormalities of the HP region. A familial case is reported: morphological anomalies of the HP region were different for both siblings. Genetic factors are evoked. CONCLUSION: The severity of the hormone deficiency is correlated to the ectopic location of the neurohypophysis, the thin appearance or non visibility of the pituitary stalk and the associated midline anomalies.     

CDK inhibitors p18(INK4c) and p27(Kip1) mediate two separate pathways to collaboratively suppress pituitary tumorigenesis

INK4 and CIP/KIP are two distinct families of cyclin-dependent kinase (CDK) inhibitors implicated in mediating a wide range of cell growth control signals. We have created p18(INK4c)-deficient mice. These mice develop gigantism and widespread organomegaly. The pituitary gland, spleen, and thymus are disproportionately enlarged and hyperplastic. T and B lymphocytes develop normally in p18-deficient mice, but both exhibit increased cellularity and a higher proliferative rate upon mitogenic stimulation. Loss of p18, like that of p27, but not other CDK inhibitor genes, leads to a gradual progression from intermediate lobe pituitary hyperplasia in young mice to an adenoma by 10 months of age with a nearly complete penetrance. Mice lacking both p18 and p27, like mice chimeric for Rb deficiency, invariably died from pituitary adenomas by 3 months. Hence, p18 and p27 mediate two separate pathways to collaboratively suppress pituitary tumorigenesis, likely by controlling the function of Rb.     

Menopause: A developmental stage, not a deficiency disease.

Proposes the view that menopause is a unique stage of development within the midlife period of reconstruction. Midlife women in therapy are viewed as a special sample of midlife women in general, and therapists are challenged to go beyond the current medical conception of menopause as a "deficiency disease." Results are reported from a survey of 157 psychotherapists concerning beliefs and clinical behaviors relating to menopause. Reflecting society's negative social construction of menopause, the data indicate that both therapists and their menopausal patients are hesitant to discuss menopause. Therapists report that most women who do discuss menopause in psychotherapy say that menopause means "getting old." The unexpected ambivalence of therapists regarding discussion of menopausal issues is analyzed in terms of countertransference issues. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

"Born from the flank"--discussion concerning "cesarean section" in animals in the Talmud

We determined growth hormone (GH) and insulin-like growth factor I (IGF-I) levels after a 3 h infusion of escalating doses of growth hormone-releasing hormone (GHRH(1-29)) followed by a bolus injection in hypopituitary patients with marked differences in pituitary features at magnetic resonance imaging (MRI) in order to evaluate further the contribution of MRI in the definition of pituitary GH reserve in GH-deficient patients. Twenty-nine patients (mean age 14.5 +/- 4.0 years) were studied. Group I comprised 13 patients: seven with isolated GH deficiency (IGHD) (group Ia) and six with multiple pituitary hormone deficiency (MPHD) (group Ib) who had anterior pituitary hypoplasia, unidentified pituitary stalk and ectopic posterior pituitary at MRI, Group II consisted of eight patients with IGHD and small anterior pituitary/empty sella, while in group III eight had IGHD and normal morphology of the pituitary gland. Growth hormone and IGF-I levels were measured during saline infusion at 08.30-09.00 h, as well as after infusion of GHRH (1-29) at escalating doses for 3h: 0.2 micrograms/kg at 09.00-10.00 h, 0.4 micrograms/kg at 10.00-11.00 h, 0.6 micrograms/kg at 11.00-12.00 h and an intravenous bolus of 2 micrograms/ kg at 12.00 h. In the group I patients, the peak GH response to GHRH(1-29) was delayed (135-180 min) and extremely low (median 2mU/l). In group II it was delayed (135-180 min), high (median 34.8 mU/l) and persistent (median 37.4 mU/l at 185-210 min). In group III the peak response was high (median 30.8 mU/l) and relatively early (75-120 min) but it declined rapidly (median 14.4 mU/l at 185-210 min). In one group I patient, GH response increased to 34.6 mU/l. The mean basal value of IGF-I levels was significantly lower in group I (0.23 +/- 0.05 U/ml) than in groups II (0.39 +/- 0.13U/ ml, p < 0.01) and III (1.54 +/- 0.46 U/ml, p < 0.001) and did not vary significantly during the GHRH(1-29) infusion. The present study demonstrates that the impaired GH response to 3 h of continuous infusion of escalating doses of GHRH(1-29) was strikingly indicative for pituitary stalk abnormality, strengthening the case for use of GHRH in the differential diagnosis of GH deficiency. The low GH response, more severe in MPHD patients, might be dependent on the residual somatotrope cells, while the better response (34.6 mU/l) in the group Ia patients might suggest that prolonged GHRH infusion could help in evaluating the amount of residual GH pituitary tissue. Pituitary GH reserve, given the GH response to GHRH infusion in GH-deficient patients with small anterior pituitary/empty sella, seems to be maintained.     

Macrotestes associated with hyperprolactinemia

Prolactin secreting pituitary adenomas are a rare finding in prepubertal children /1/. As in adults, their incidence is higher in girls than in boys; however, the macroadenomas are predominant in boys /20-16/. Two prepubertal boys who presented with short stature and linear growth deceleration were diagnosed to have prolactin secreting pituitary macroadenoma associated with growth hormone (GH) deficiency. They were treated with bromocryptine and exogenous recombinant hGH. They achieved a normal adult stature, full sexual maturation and tumor regression on the therapy. In addition, both boys developed macrotestes. Further evaluation ruled out other etiologies for macrotestes. We presume that the elevated prolactin caused local testicular growth factors to induce testicular cell division and/or hypertrophy resulting in an increased testicular volume.     

Management of hyperprolactinaemic amenorrhoea

Results of treatment of 52 patients with amenorrhoea associated with hyperprolactinaemia are presented. All patients had a detailed radiological examination of the pituitary fossa, including lateral tomography in every patient and air encephalography in those in whom a pituitary tumour was suspected. There were 17 patients with untreated pituitary tumours, 5 patients with previously treated pituitary tumours and persisting hyperprolactinaemia, and 30 patients with normal pituitary radiology. Patients with pituitary tumours were treated either by transsphenoidal or transfrontal surgical extirpation of the tumour, followed, if necessary, by external irradiation and/or bromocriptine, Four patients were treated with external irradiation as primary therapy, and three patients who did not wish to conceive were treated with bromocriptine as primary therapy. Patients with normal radiological appearances were treated with bromocriptine as primary treatment. Ovulatory menstrual cycles developed in 42 patients and there were 19 pregnancies. Those ovulating but not conceiving had adequate nonendocrine factors to account for the disparity. Failure of response was seen in 10 patients and was due to inadequate fall of prolactin in response to surgery (2 patients), external irradiation (3 patients) and bromocriptine (1 patient), and gonadotrophin deficiency which developed after surgery in 3 patients but was present pre-operatively in 1. The relative merits of treatment by surgery, external irradiation and bromocriptine are discussed and a policy of treatment outlined.     

Cryotherapy in the treatment of spring conjunctivitis

A 15-year-old boy had growth failure and failure of sexual development. The probable onset was at age 10. Endocrine studies showed hypopituitarism with deficiency of growth hormone and follicle-stimulating hormone, an abnormal response to metyrapone, and deficiency of thyroid function. Luteinizing hormone level was in the low-normal range. Posterior pituitary function was normal. Roentgenogram showed a large sella with some destruction of the posterior clinoids. Transsphenoidal exploration was carried out. The sella was empty except for a whitish membrane; no pituitary tissue was seen. The sella was packed with muscle. Recovery was uneventful, and the patient was given replacement therapy. On histologic examination,the cyst wall showed low pseudostratified cuboidal epithelium and occasional squamous metaplasia. Hemosiderin-filled phagocytes and acinar structures were also seen. The diagnosis was probable rupture of an intrasellar epithelial cyst, leading to empty sella syndrome.     

The distribution of p75 neurotrophin receptor-immunoreactive cells in the forebrain of the common marmoset (Callithrix jacchus)

Cyclooxygenase (COX) is the rate-limiting enzyme in the synthesis of prostaglandins (PGs) and exists in two isoforms, COX-1 and COX-2. In spite of long-standing speculation, definitive roles of PGs in various events of early pregnancy remain elusive. We demonstrate herein that the targeted disruption of COX-2, but not COX-1, in mice produces multiple failures in female reproductive processes that include ovulation, fertilization, implantation, and decidualization. Using multiple approaches, we conclude that these defects are the direct result of target organ-specific COX-2 deficiency but are not the result of deficiency of pituitary gonadotropins or ovarian steroid hormones, or reduced responsiveness of the target organs to their respective hormones.     

18p monosomy with GH-deficiency and empty sella: good response to GH-treatment

A patient with 18p monosomy and GH deficiency due to pituitary hypoplasia, who showed an excellent response to GH-treatment, is described. Patients with this syndrome should be considered for endocrine evaluation, as they can benefit from hormonal substitution.     

Multiple pituitary hormone deficiencies in a patient with spinocerebellar ataxia: magnetic resonance imaging and hormonal studies

Degenerative spinocerebellar ataxia has a rare association with hypogonadotropic hypogonadism. In this report we present the results of the detailed endocrine evaluation and magnetic resonance imaging in one such patient. A 20-year-old male with progressive cerebellar ataxia, hypogonadism, and short stature was investigated. Basal testing revealed hypogonadotropic hypogonadism (LH < 5 mU/L, FSH < 5 mU/L, testosterone 2.5 nM/L). There was no rise in LH after stimulation with LHRH, peak LH level being < 5 mU/L. Insulin hypoglycemia testing was consistent with GH deficiency, with peak GH being 3.2 mU/L. On TRH stimulation, there was no significant rise in prolactin, though the TSH response was normal. Magnetic resonance imaging revealed cerebellar atrophy. The anterior pituitary was atrophic, with a height of 1.4 mm. The posterior pituitary and the pituitary stalk were normal in size and position. This patient with degenerative spinocerebellar ataxia had multiple pituitary hormone deficiencies. The results of our endocrine evaluation and MR imaging lead us to believe that these deficits may result from a lesion at the level of the pituitary gland.     

Mice deficient in both p53 and Rb develop tumors primarily of endocrine origin

To examine whether a cooperative role exists between inherited Rb and p53 deficiency in tumorigenesis, crosses were made between p53- and Rb-deficient mice and were monitored for subsequent tumor incidence and spectrum. Parental mice containing either Rb or p53 mutant alleles showed a predisposition for pituitary adenomas or lymphomas and sarcomas, respectively. Mice heterozygous for both Rb and p53 mutant alleles developed tumors of endocrine origin (medullary thyroid carcinomas, pancreatic islet cell carcinomas, and pituitary adenomas) in addition to lymphomas and sarcomas. Except for pituitary adenomas, these endocrine tumors were rarely seen in the parental p53 or Rb mutant mice. Mice deficient for both Rb and p53 showed a faster rate of tumor development than mice deficient only in Rb or p53. These results indicate that p53 and Rb do cooperate in the acceleration of tumorigenesis and in the development of endocrine tumor types.     

Divergent expression of alpha1-protease inhibitor genes in mouse and human

The alpha1-protease inhibitor proteins of laboratory mice are homologous in sequence and function to human alpha1-antitrypsin and are encoded by a highly conserved multigene family comprised of five members. In humans, the inhibitor is expressed in liver and in macrophages and decreased expression or inhibitory activity is associated with a deficiency syndrome which can result in emphysema and liver disease in affected individuals. It has been proposed that macrophage expression may be an important component of the function of human alpha1-antitrypsin. Clearly, it is desirable to develop a mouse model of this deficiency syndrome, however, efforts to do this have been largely unsuccessful. In this paper, we report that aside from the issues of potentially redundant gene function, the mouse may not be a suitable animal for such studies, because there is no significant expression of murine alpha1-protease inhibitor in the macrophages of mice. This difference between the species appears to result from an absence of a functional macrophage-specific promoter in mice.