Eleven-Year Experience with Selective Adrenal Vein Sampling in Management of Primary Adrenal Hormonal Hypersecretion.

Introduction: Nearly half of the adult population in the United States has been diagnosed with hypertension. Adrenal hormonal hypersecretion is a leading cause of secondary hypertension. Adrenal vein sampling (AVS) may assist in differentiating between unilateral and bilateral adrenal hormonal hypersecretion to identify patients who are candidates for adrenalectomy. We reviewed the use of AVS at our institution along with associated outcomes after adrenalectomy. Materials and Methods: A retrospective chart review was conducted of patients with a diagnosis of primary hyperaldosteronism (PA) or adrenocorticotropic hormone-independent Cushing syndrome (AICS) and who underwent adrenalectomy between January 1, 2010, and December 1, 2021. Patient data of baseline characteristics, preoperative workup, including AVS, and postoperative outcomes were collected and analyzed. Results: Seventy-one patients were identified in the study period (48 PA and 23 AICS). Computed tomography scan identified unilateral adrenal nodules in 52 patients (29 left; and 23 right), bilateral nodules in 13 patients, and no nodules in 6 patients. AVS was performed in 45 patients with PA (93%) and 5 patients with AICS (21%). After surgery, the number of PA patients with hypokalemia or requiring potassium supplementation significantly decreased after adrenalectomy (before surgery: 33 [68.7%]; and after surgery: 5 [10.4%], P < .01). The number of medications required for hypertension in AICS patients also significantly decreased. No major adverse events were noted. Conclusions: Our long-term experience demonstrates the ongoing use of AVS during workup of patients with primary hyperaldosteronism and for select patients with adrenocorticotropic hormone-independent Cushing syndrome. However, a low level of discordance between imaging and AVS findings in PA patients suggests that there may be a subset of patients in whom preoperative AVS is not necessary.

Successful percutaneous CT-guided microwave ablation of adrenal gland for ectopic Cushing syndrome.

Adrenocorticotropic hormone production by pancreatic neuroendocrine tumor (PNET) is rare and results in hyperstimulation of the adrenal gland to produce ectopic Cushing syndrome. Our case showcases the safety and effectiveness of percutaneous CT-guided microwave ablation of the adrenal gland in a 49-year-old female with PNET and hepatic metastases who presented with ectopic Cushing syndrome despite surgical resection of the primary pancreatic tumor and left adrenal gland. Prior to ablation, the right adrenal gland measured 4.3×1.6×2.0cm and the patient had malignant hypertension with elevated morning serum cortisol level (1976nmol/L). After microwave ablation of the right adrenal gland, the hypertension resolved and the cortisol level decreased dramatically (74nmol/L). As expected after successful treatment, the patient developed adrenal insufficiency and was placed on glucocorticoid and mineralocorticoid supplementation.

Vitamin D status before and after hypophysectomy in dogs with pituitary-dependent hypercortisolism.

Both spontaneous hypercortisolism and chronic glucocorticoid treatment are associated with osteoporosis and low circulating concentrations of 1,25-dihydroxy-vitamin D in humans. Pituitary-dependent hypercortisolism (PDH) is a common disorder in dogs, but little is known about the vitamin D status of affected dogs. Pituitary-dependent hypercortisolism in dogs can be treated effectively by hypophysectomy and subsequent hormone supplementation. Because hormone supplementation does not include GH, dogs that have undergone hypophysectomy have low circulating concentrations of GH and IGF-1, which may result in low plasma 1,25-dihydroxy-vitamin D concentrations and consequently increased parathyroid hormone secretion. The aim of this study was to determine whether dogs with PDH need vitamin D supplementation before and/or after hypophysectomy. To this end, we measured plasma concentrations of GH, IGF-1, parathyroid hormone, calcium, phosphate, and vitamin D metabolites in 12 dogs with PDH before and 8 wk after hypophysectomy and in 12 control dogs. Although plasma GH concentrations were lower in dogs with PDH than in control dogs both before and after hypophysectomy, the vitamin D status was similar. In conclusion, there is no need for vitamin D supplementation in dogs with PDH, either before or after hypophysectomy.

Unilateral adrenalectomy can be an alternative therapy for infantile onset Cushing' s syndrome caused by ACTH-independent macronodular adrenal hyperplasia with McCune-Albright syndrome.

We report herein the case of a 1-year-old boy with McCune-Albright syndrome (MAS) who presented with infantile-onset Cushing' s syndrome caused by ACTH independent macronodular adrenal hyperplasia (AIMAH). Abdominal CT, MRI, and adrenal scintigraphy with (131)I-adosterol identified bilateral adrenal involvement with the left adrenal gland being larger and functionally more active. Unilateral adrenalectomy of the left gland was performed and ameliorated many clinical symptoms, such as Cushingoid appearance and height restriction, and it also normalized many endocrinological data, such as diurnal rhythms of ACTH and cortisol, ACTH and cortisol responses to CRH, and urinary 24 hr free cortisol. Glucocorticoid was replaced for the first 1 year and 6 months after the operation. One adrenal crisis episode occurred at 3 weeks after the operation, but none have occurred since. These results suggest that unilateral adrenalectomy of the larger gland can be an alternative therapy for infantile onset Cushing' s syndrome caused by AIMAH with MAS, when asymmetric involvement is evident and the smaller gland is not markedly enlarged.

Symptomatic hypercalcemia due to painless thyroiditis after unilateral adrenalectomy in a patient with Cushing's syndrome.

We report a 53-year-old woman with Cushing's syndrome due to an adrenocortical adenoma, who underwent unilateral adrenalectomy and developed symptomatic hypercalcemia during the thyrotoxic period of painless thyroiditis, while tapering off a daily supplemented dose of cortisol. A study of patients with thyrotoxicosis and hypoadrenalism at our institute revealed that mild hypercalcemia was present in 9.9% of those with thyrotoxicosis and 5.0% of those with hypoadrenalism. The present case suggests that the simultaneous occurrence of thyrotoxicosis and hypoadrenalism may lead to overt hypercalcemia due to a synergistic increase in bone resorption and impaired urinary excretion of calcium.

Ketoconazole therapy: an efficacious alternative to achieve eucortisolism in patients with Cushing's syndrome.

Cushing's syndrome (CS) is a serious condition requiring drug management in diverse clinical settings. Fifty four patients (44 females, 10 males) with CS, aged 14-63, received ketoconazole (KTZ) prior to surgery (n= 27), as complementary therapy after surgery and/or radiotherapy (n= 16), or as primary treatment (n= 11). It was given at a 600 (500 - 600) mg/day (median - Cl195) maintenance dose for periods ranging from 15 days to 13 years. Clinical signs, hepatic enzymes and urinary free cortisol (UFC) were evaluated before and during KTZ treatment. UFC normalised or decreased to subnormal values in 85% of the patients, in 5 to 150 days after starting treatment; although failing to normalise, UFC decreased to 12-48% of pre-treatment values in the remaining patients. Clinical signs improved throughout. Side effects were adrenal insufficiency (18.5%), reversible hepatic toxicity (11%), allergic skin rash (5.5%) and gastric intolerance (3.7%); in 11% of patients, an "escape phenomenon" was observed. Twenty-four out of the total (44.4%) were treated for prolonged periods, from one up to 13 years. In conclusion, this study confirms that KTZ is an effective and generally well tolerated treatment for CS particularly: a) shortly before surgery, b) because of persistent hypercortisolism after surgery or awaiting the results of radiotherapy, c) as a reasonable option in patients with CS of unknown aetiology and, d) as long-term therapy in any case of unsolved hypercortisolism after failure of current treatments.

[Anaesthesia for patients with adrenal gland diseases]. / Anästhesie bei Erkrankungen der Nebennierenrinde--Effizientes Risikomanagement von der Prämedikation bis zum Aufwachraum.

Perioperative management of patients with adrenal gland diseases requires detailed information on the individual endocrine status and the potential complications. Typical signs of primary hyperaldosteronism (Conn's syndrome) comprise arterial hypertension, hypokalaemia and metabolic alkalosis. In such cases preoperative treatment with spironolactone is highly recommended. In patients with hypercortisolism (Cushing's syndrome) the following concomitant disorders must be considered particularly: arterial hypertension, osteoporosis, vulnerable skin, diabetes mellitus, and increased risk for infection and thromboembolism. In all patients with proven or suspected adrenocortical insufficiency (i.e. Addison's disease, after removal of a cortisol producing tumour or as the result of long-term therapy with glucocorticoids) consequent perioperative supplementation of hydrocortisone is mandatory. In patients with phaeochromcytoma hypertensive crisis and tachyarrhythmias may occur intraoperatively resulting from massive catecholamine release. Thus, preoperative treatment with the beta-antagonist phenoxybenzamine is obligatory. In contrast, nitroprusside is the substance of choice for intraoperative control of blood pressure. beta-blocking agents may be used in phaeochromocytoma but only under sufficient beta-blockade. Removal of a malignant tumour of the adrenal gland may induce massive haemorrhage, and thus anaesthetic management has to be modified.

Ketoconazole therapy: an efficacious alternative to achieve eucortisolism in patients with Cushings syndrome

El síndrome de Cushing (SC) es un trastorno grave que requiere frecuentemente tratamiento medicamentoso. Cincuenta y cuatro pacientes (44 mujeres, 10 varones) de 14-63 años de edad con SC, recibieron ketoconazol (KTZ) previo a cirugía (n=27), como complemento luego de cirugía y/o radioterapia (n=16), o como tratamiento primario (n=11). La dosis de mantenimiento fue de 600 (500 - 600) mg/día (mediana-IC95) durante 15 días a 13 años. Los signos clínicos, hepatograma y cortisol libre urinario (CLU) fueron evaluados antes y durante tratamiento con KNZ. El CLU cayó a valores normales o subnormales en 85% de los pacientes, 5 a 150 días luego de iniciar el tratamiento; aún sin normalizar, el CLU disminuyó a 12-48% de los valores pre-tratamiento en el resto de los pacientes acompañándose de mejoría de los signos clínicos. Los efectos colaterales fueron: insuficiencia adrenal (18.5%), toxicidad hepática reversible (11%), "rash" cutáneo (5.5%) e intolerancia gástrica (3.7%); en 11% de los pacientes se observó un fenómeno de "escape". Veinticuatro pacientes (44.4%) fueron tratados por períodos prolongados, de uno a trece años. Este estudio confirma que el KTZ constituye un tratamiento eficaz y generalmente bien tolerado del SC, en particular: a) como preparación para cirugía b) en casos de hipercortisolismo residual luego de cirugía o en espera de resultados de radioterapia, c) como una alternativa razonable en pacientes con SC de origen desconocido y, d) como tratamiento crónico en casos de hipercortisolismo no resuelto luego de fracaso de las terapéuticas habituales.(AU)

Cushings syndrome (CS) is a serious condition requiring drug management in diverse clinical settings. Fifty four patients (44 females, 10 males) with CS, aged 14-63, received ketoconazole (KTZ) prior to surgery (n= 27), as complementary therapy after surgery and/or radiotherapy (n= 16), or as primary treatment (n= 11). It was given at a 600 (500 - 600) mg/day (median - CI95) maintenance dose for periods ranging from 15 days to 13 years. Clinical signs, hepatic enzymes and urinary free cortisol (UFC) were evaluated before and during KTZ treatment. UFC normalised or decreased to subnormal values in 85% of the patients, in 5 to 150 days after starting treatment; although failing to normalise, UFC decreased to 12-48% of pre-treatment values in the remaining patients. Clinical signs improved throughout. Side effects were adrenal insufficiency (18.5%), reversible hepatic toxicity (11%), allergic skin rash (5.5%) and gastric intolerance (3.7%); in 11% of patients, an "escape phenomenon" was observed. Twenty-four out of the total (44.4%) were treated for prolonged periods, from one up to 13 years. In conclusion, this study confirms that KTZ is an effective and generally well tolerated treatment for CS particularly: a) shortly before surgery, b) because of persistent hypercortisolism after surgery or awaiting the results of radiotherapy, c) as a reasonable option in patients with CS of unknown aetiology and, d) as long-term therapy in any case of unsolved hypercortisolism after failure of current treatments.(AU)

Ketoconazole therapy: an efficacious alternative to achieve eucortisolism in patients with Cushing's syndrome

El síndrome de Cushing (SC) es un trastorno grave que requiere frecuentemente tratamiento medicamentoso. Cincuenta y cuatro pacientes (44 mujeres, 10 varones) de 14-63 años de edad con SC, recibieron ketoconazol (KTZ) previo a cirugía (n=27), como complemento luego de cirugía y/o radioterapia (n=16), o como tratamiento primario (n=11). La dosis de mantenimiento fue de 600 (500 - 600) mg/día (mediana-IC95) durante 15 días a 13 años. Los signos clínicos, hepatograma y cortisol libre urinario (CLU) fueron evaluados antes y durante tratamiento con KNZ. El CLU cayó a valores normales o subnormales en 85% de los pacientes, 5 a 150 días luego de iniciar el tratamiento; aún sin normalizar, el CLU disminuyó a 12-48% de los valores pre-tratamiento en el resto de los pacientes acompañándose de mejoría de los signos clínicos. Los efectos colaterales fueron: insuficiencia adrenal (18.5%), toxicidad hepática reversible (11%), "rash" cutáneo (5.5%) e intolerancia gástrica (3.7%); en 11% de los pacientes se observó un fenómeno de "escape". Veinticuatro pacientes (44.4%) fueron tratados por períodos prolongados, de uno a trece años. Este estudio confirma que el KTZ constituye un tratamiento eficaz y generalmente bien tolerado del SC, en particular: a) como preparación para cirugía b) en casos de hipercortisolismo residual luego de cirugía o en espera de resultados de radioterapia, c) como una alternativa razonable en pacientes con SC de origen desconocido y, d) como tratamiento crónico en casos de hipercortisolismo no resuelto luego de fracaso de las terapéuticas habituales.

Cushing's syndrome (CS) is a serious condition requiring drug management in diverse clinical settings. Fifty four patients (44 females, 10 males) with CS, aged 14-63, received ketoconazole (KTZ) prior to surgery (n= 27), as complementary therapy after surgery and/or radiotherapy (n= 16), or as primary treatment (n= 11). It was given at a 600 (500 - 600) mg/day (median - CI95) maintenance dose for periods ranging from 15 days to 13 years. Clinical signs, hepatic enzymes and urinary free cortisol (UFC) were evaluated before and during KTZ treatment. UFC normalised or decreased to subnormal values in 85% of the patients, in 5 to 150 days after starting treatment; although failing to normalise, UFC decreased to 12-48% of pre-treatment values in the remaining patients. Clinical signs improved throughout. Side effects were adrenal insufficiency (18.5%), reversible hepatic toxicity (11%), allergic skin rash (5.5%) and gastric intolerance (3.7%); in 11% of patients, an "escape phenomenon" was observed. Twenty-four out of the total (44.4%) were treated for prolonged periods, from one up to 13 years. In conclusion, this study confirms that KTZ is an effective and generally well tolerated treatment for CS particularly: a) shortly before surgery, b) because of persistent hypercortisolism after surgery or awaiting the results of radiotherapy, c) as a reasonable option in patients with CS of unknown aetiology and, d) as long-term therapy in any case of unsolved hypercortisolism after failure of current treatments.

Hemodynamic responses to epinephrine-containing local anesthetic injection and to emergence from general anesthesia in transsphenoidal hypophysectomy patients.

Patients undergoing transsphenoidal pituitary surgery may experience hypertensive episodes during the intranasal injection of vasoconstrictor-supplemented local anesthetics or emergence from general anesthesia. The present research characterized the blood pressure responses during transsphenoidal surgery and tested the hypothesis that the underlying pituitary disease influences the incidence and magnitude of the blood pressure responses. The records of 100 patients were retrospectively reviewed. All had direct blood pressure measurements recorded using a computer-based anesthesia recording system. Mean age was 49 +/- 17 years (+/- SD) and 52% were male. Blood pressure increased by 60 +/- 37 mm Hg systolic and 23 +/- 22 mm Hg diastolic with intranasal injection and 42 +/- 24 mm Hg systolic and 23 +/- 16 mm Hg diastolic during emergence from general anesthesia. Systolic blood pressure increased by greater than 50% in 58% of patients following intranasal injection and in 33% of patients upon emergence from anesthesia. Blood pressure responses did not differ with respect to endocrinopathy type (Cushing's disease, acromegaly, or other pathology), gender, age, surgeon, history of prior transsphenoidal surgery, history of either hypertension or diabetes, or preoperative use of either beta-adrenergic or calcium channel-blocking drugs. There was poor correlation between the epinephrine dose injected (range 30-220 microg) and systolic blood pressure response (r = 0.24; r2 = 0.06; P = 0.031). Blood pressure increases were not associated with cardiac arrhythmias, persistent myocardial ischemia, or myocardial infarction. The authors conclude that in transsphenoidal hypophysectomy patients, large blood pressure increases are common with intranasal injection and upon awakening from general anesthesia. However, the authors were not able to find a variable that might enable the prediction of which patients are most likely to experience the most intense blood pressure elevations.

Contraceptive pills induce an improvement in congenital hypoplasminogenemia in two unrelated patients with ligneous conjunctivitis.

Severe type I plasminogen deficiency is the underlying cause of ligneous conjunctivitis, a rare disease characterized by wood-like pseudomembranes developing on the ocular and extraocular mucosa. Two unrelated female patients with ligneous conjunctivitis and moderate hypoplasminogenemia are described. Being of fertile age, they were treated with oral contraceptives, which determined a marked increase in plasminogen levels. Moreover, a palpebral pseudomembrane stopped growing in one patient and disappeared completely in the other while on the estroprogestinic treatment. In patient n. 2, who also suffered from von Willebrand's disease, prior Cushing's disease induced an increase in both von Willebrand factor and plasminogen levels, which dropped after curative hypophysectomy. Genetic plasminogen study showed a 19Lys>Glu mutation in a heterozygous state in the first proposita and in a homozygous state in the second proband. In addition, both index patients were homozygous for a new intron F-14T>G mutation, which was found to reduce the acceptor splicing site prediction score. In conclusion, oral contraceptive therapy may improve plasminogen deficiency and deserves attention as an alternative therapeutic approach in selected cases of ligneous conjunctivitis with low, but not absent, plasminogen synthesis.

Pituitary corticotroph adenoma containing many apoptotic cells: a histologic, immunohistochemical, ultrastructural and molecular study.

Apoptosis regulates cell turnover in normal tissues and occurs during the neoplastic process. Owing to difficulties in recognizing apoptotic cells by histology alone, several complementary approaches have been introduced, which disclosed the presence of cells with typical nuclear and cytoplasmic changes characteristic of apoptosis. Electron microscopy remains the most conclusive method to reveal the structural changes. Identification of caspase cleaved keratin 18 intermediate filament rearrangements can contribute to the identification of early apoptotic changes. The authors present here an unusual case of a pituitary corticotroph adenoma removed surgically from a young woman with Cushing disease. The tumor contained many apoptotic cells identified by histology. In addition, the apoptotic events were investigated using various morphologic techniques, including electron microscopy, the in situ end-labeling technique, and immunohistochemistry to confirm the caspase-cleaved keratin 18 rearrangements.

Síndrome de Cushing por secreción ectópica de ACTH: análisis del mecanismo fisiopatológico de la hipokalemia: comunicación de dos casos / Cushing syndrome with severe hipokalemia caused by ectopic ACTH secretion: report of two cases

We report a 42 years old male and a 66 years old female with a Cushing syndrome caused by ectopic ACTH secretion secondary to a carcinoid tumor. These patients had both severe hypokalemia, resistant to medical treatment and that subsided with bilateral adrenalectomy and supplementation with dexametasone. Cushing syndrome caused by ectopic ACTH secretion is characterized by a severe and rapidly evolving hypercortisolism. Hypokalemia is present in 90 percent of cases and is probably caused by a defect in 11 ß hydroxysteroid dehydrogenase, that limits the binding of cortisol to aldosterone receptor, metabolizing it to cortisone. Therefore, this alteration will increase the mineralocorticoid action of cortisol

The pituitary corticotroph is not the rate limiting step in the postoperative recovery of the hypothalamic-pituitary-adrenal axis in patients with Cushing syndrome.

Patients cured from endogenous Cushing syndrome usually develop postoperative adrenal suppression in the year ensuing surgery. To define whether the pituitary corticotroph is the rate limiting step in the postoperative recovery of this secondary/tertiary form of adrenal insufficiency, we examined surgically cured patients with Cushing syndrome 10 days, 3 months, and 6-12 months after surgery, by administering ovine CRH (oCRH) iv at the dose of 1 microgram/kg.h over 24 h. The pituitary corticotroph of these patients responded vigorously to oCRH, with ACTH concentrations reaching above the normal range at all three times of testing. Parallel measurements of cortisol in nonadrenalectomized patients demonstrated subnormal adrenal responsiveness at 10 days and 3 months and normalization at 6-12 months after surgery. The circadian rhythm of ACTH was maintained postoperatively at 10 days and 6-12 months, and the circadian rhythm of cortisol was also present at 6-12 months after surgery, in spite of the constant infusions of pharmacological doses of oCRH, suggesting that factors other than CRH secretion regulate this rhythm. We conclude that the corticotroph is not the rate limiting step in the recovery of the hypothalamic-pituitary-adrenal axis from glucocorticoid-induced adrenal suppression, and that the locus of the defect resides in the hypothalamic CRH neuron and/or its higher regulatory inputs.

Case report: silent thyroiditis after adrenalectomy in a patient with Cushing's syndrome.

A case of silent thyroiditis after unilateral adrenalectomy for treatment of Cushing's syndrome is reported. The left adrenocortical adenoma was resected. Glucocorticoid was replaced after the operation and was gradually tapered. Thyrotoxic symptoms with painless goiter occurred 9 months after the adrenalectomy when a replacement dose of prednisolone was tapered to 5 mg/d. Plasma-free thyroid hormones increased and thyrotropin was suppressed. Thyroidal uptake of radioactive iodine was extremely low. Both titers of antimicrosomal and antithyroglobulin antibodies stayed at high levels throughout the observation period from the preoperative stage. Normalization of thyroid functions was obtained 3 months after the onset of thyrotoxicosis with beta-adrenergic blocker alone. It was speculated that exposure to a large amount of endogenous and supplementary exogenous glucocorticoid protected the patient's immune system from autoimmune attack of thyroid antigens and that tapering of the supplementary glucocorticoid caused exacerbation of immune responses, resulting in overt thyroid dysfunction even 9 months after adrenalectomy.

Diagnosis and management of ACTH-dependent Cushing's syndrome: comparison of the features in ectopic and pituitary ACTH production.

The clinical features, diagnosis and management of 16 consecutive patients with ectopic ACTH production are described and biochemical data are compared with those of 48 consecutive patients with pituitary-dependent Cushing's disease. In 10 cases the ectopic ACTH secreting tumour was completely occult to routine clinical and radiological investigation, and no basal or dynamic investigation of adrenal-pituitary function was able clearly to differentiate these patients from those with Cushing's disease. High dose dexamethasone suppression testing assessed by plasma cortisol was usually helpful but unexpected responses were seen in both diagnostic groups; the metyrapone test yielded no useful information and should now be abandoned. Hypokalaemia was seen in all patients with ectopic ACTH production but in only 10% of those with Cushing's disease who were not on diuretics at presentation. Successful diagnosis and tumour localization was most frequently achieved by a combination of CT scanning of the chest and abdomen and venous catheter sampling for ACTH. All patients in whom the ectopic ACTH-secreting tumour was obvious at presentation died of their primary tumour within 8 months, whereas seven of the 10 patients with occult tumours at presentation are alive 1.5-16.5 years later, and appear cured. Occult ectopic ACTH secretion may be impossible to distinguish from pituitary Cushing's disease. Multiple and repeated investigations are often required to make this differential diagnosis, essential for appropriate therapy.

[Cushing's disease. Current data on its course and treatment]. / Maladie de Cushing. Données actuelles sur l'évolution et le traitement.

Recent developments in the treatment of Cushing's disease, particularly the trans-sphenoidal microadenomectomy, have prompted a survey of the pathophysiological theories of ACTH hypersecretion in this condition. The results of the trans-sphenoidal approach are reported and the post-surgical evolution (success failure or recurrence) are discussed. It is emphasized that a long fellow up is essential to assess the efficacy of this therapeutic approach.

Metabolic response to two-stage adrenalectomy ih patients with Cushing's disease.

In 5 patients with Cushing's disease the balance of nitrogen, potassium, phosphorus, sodium and chlorides was determined during 5 days before, and 10 days after bilateral two-stage adrenalectomy. The patients received substitute treatment with hydrocortisone in mean doses of 112 mg/24 hours after the first stage and 203 mg/24 hours after the second stage. After removal of the first adrenal the metabolic response of the cell mass and extracellular space was within the normal range of moderately intense responses. After the second adrenalectomy the cumulative balance of the components of the cell mass was slightly negative and retention of sodium and chlorides was more pronounced than after the first operation.

Postadrenalectomy pituitary adenoma (Nelson's syndrome) in childhood: clinical and roentgenologic detection.

Following total adrenalectomy in Cushing's syndrome associated with adrenal hyperplasia, but not with adrenal adenoma or malignancy, elements of the pituitary may be stimulated to grow rapidly and even aggressively. There is strong evidence to support the idea that there is a pre-existing tumor in many, if not all, of these cases. In some, the tumor may be too small to deform the sella turcica. After adrenalectomy, these patients should be observed carefully and frequently for hyperpigmentation, visual field defects, and sella turcica enlargement.