Philip C. Johnston

Factors Associated With Islet Yield and Insulin Independence After Total Pancreatectomy and Islet Cell Autotransplantation in Patients With Chronic Pancreatitis Utilizing Off-site Islet Isolation: Cleveland Clinic Experience

CONTEXT Total pancreatectomy (TP) with islet cell autotransplantation (IAT) can reduce or prevent diabetes by preserving beta cell function and is normally performed with on-site isolation laboratory facilities. OBJECTIVE We examined factors associated with islet yield and metabolic outcomes in patients with chronic pancreatitis undergoing TP-IAT. We report our experience of TP-IAT with an off-site islet isolation laboratory. PATIENTS AND METHODS Data (August 2008 to February 2014) were obtained from a TP-IAT database which included information from medical records, clinic visits, questionnaires, and follow-up telephone calls. Each patient was assessed with pre- and postoperative 5-hour mixed-meal tolerance tests for metabolic measurements and with serial glycosylated hemoglobin (HbA1c) determinations. RESULTS Thirty-six patients with a mean age of 38 years (range, 16-72 y) underwent TP-IAT for different etiologies. At a median follow-up time of 28 months (range, 3-66 mo), 12 patients were insulin independent and 24 patients were on at least one insulin injection a day. Postoperatively, C-peptide levels ≥0.3 ng/mL were present in 23/33 (70%) of the patients, with a median fasting C-peptide value of 0.8 ng/mL (range, <0.2-1.5 ng/mL). Those who were insulin independent were more likely to be female (P = .012), have normal morphology on pre-operative pancreatic imaging (P = .011), and have significantly higher median islet yield (6845 islet equivalent numbers [IEQ]/kg, n = 12 vs 3333 IEQ/kg, n = 24; P < .001). CONCLUSIONS IAT after TP performed in our facility with an off-site islet isolation laboratory shows islet yield and rates of insulin independence that are comparable to other large centers with on-site laboratories.

Lymphocytic infundibulo-neurohypophysitis: a clinical overview

Lymphocytic infundibulo-neurohypophysitis is an uncommon inflammatory disorder postulated to be autoimmune in origin. Because of the location of inflammation, it selectively affects the posterior lobe of the pituitary (neurohypophysis) and pituitary stalk (infundibulum). The most common presentation is central diabetes insipidus. Although the definitive diagnosis is established histologically by a pituitary biopsy, radiological imaging can be valuable in diagnosing this condition. In this paper, we provide an overview of the pathophysiology, investigations, management, and outcomes of lymphocytic infundibulo-neurohypophysitis.

Pituitary tumor apoplexy

We review the etiology, investigations, management and outcomes of pituitary tumor apoplexy. Pituitary tumor apoplexy is a clinical syndrome which typically includes the acute onset of headache and/or visual disturbance, cranial nerve palsy and partial or complete endocrine dysfunction. It is associated with either infarction or hemorrhage of a pre-existing pituitary adenoma and is associated with significant morbidity and potential fatality. Not all patients will present with classic signs and symptoms, therefore it is pertinent to appreciate the clinical spectrum in which this condition can present.

Intra-articular glucocorticoid injections and their effect on hypothalamic–pituitary–adrenal (HPA)-axis function

The use of intra-articular (IA) glucocorticoids for reducing pain and inflammation in patients with osteoarthritis, rheumatoid arthritis, and other inflammatory arthropathies is widespread among primary care physicians, specialists, and non-specialists in the United States. Injectable glucocorticoids have anti-inflammatory and analgesic properties which can be effective in improving clinical parameters such as pain, range of motion, and quality of life. After injection into the IA space, glucocorticoids may be systemically absorbed; the degree of absorption can depend on the size of the joint injected, the injectable glucocorticoid preparation used, the dosage, and the frequency of the injection. The adverse effects of intra-articular glucocorticoid injections (IAGC) can often be overlooked by both the patient and physicians who administer them, in particular the potential deleterious effect on the hypothalamic–pituitary−adrenal (HPA)-axis which can result in adrenal suppression and/or iatrogenic Cushing syndrome. In this paper we provide an overview on the often under-recognized effects of IAGC on HPA-axis function.

Ectopic ACTH-secreting pituitary adenomas within the sphenoid sinus

Ectopic pituitary adenomas are defined by the presence of adenomatous pituitary tissue outside the sella and distinctly separate from the pituitary gland. Ectopic ACTH-secreting pituitary adenomas (EAPAs) are a rare cause of Cushing’s syndrome. Detecting these radiologically can prove difficult, in part, due to their typically small size and unpredictable anatomical location. In ACTH-dependent Cushing’s syndrome, if, despite comprehensive testing, the source of excess ACTH remains occult (including negative work up for ectopic ACTH syndrome) thought should be given to the possibility of the patient harboring an EAPA. In most cases, ectopic ACTH pituitary adenomas within the sphenoid sinus will manifest with symptoms of hormonal excess, have an obvious sphenoid sinus mass on pre-operative imaging and will demonstrate resolution of hypercortisolism after surgical excision if located and removed. Twenty cases of EAPAs have been reported in the literature to date. This paper will review the current literature on all previously reported EAPAs within the sphenoid sinus in addition to the current case.

Surgical management of recurrent Cushing′s disease in pregnancy: A case report

Background: Cushings disease is a condition rarely encountered during pregnancy. It is known that hypercortisolism is associated with increased maternal and fetal morbidity and mortality. When hypercortisolism from Cushings disease does occur in pregnancy, the impact of achieving biochemical remission on fetal outcomes is unknown. We sought to clarify the impact of successful surgical treatment by presenting such a case report. Case Description: A 38-year-old pregnant woman with recurrent Cushings disease after 8 years of remission. The patient had endoscopic transsphenoidal of her pituitary adenoma in her 18th week of pregnancy. The patient had postoperative biochemical remission and normal fetal outcome with no maternal complications. Conclusion: Transsphenoidal surgery for Cushings disease can be performed safely during the second trimester of pregnancy.

Variability of Late-Night Salivary Cortisol in Cushing Disease: A Prospective Study

Background The frequency of variable hormonogenesis in patients with Cushing disease (CD) but without cyclical symptoms is unclear. Aim To assess the frequency of variable hormonogenesis in patients presenting with CD. Methods Over a 6-month period, patients with confirmed or suspected CD provided late-night salivary samples for up to 42 consecutive nights. Results Of 19 patients confirmed to have CD, 16 provided at least 7 consecutive salivary samples, and 13 provided at least 21; these 16 patients are the subjects of this report. Twelve patients had at least three peak and two trough levels of late-night salivary cortisol (LNSC) but in only two patients were strict criteria for cyclical hormonogenesis fulfilled; variation was assessed as random in the others. Eight patients had de novo CD, and eight had recurrent/persistent disease. All patients with recurrent/persistent CD had two or more normal results, and in four of these patients, >50% of LNSC were normal. In six patients with de novo disease with at least one normal LNSC level, the maximum levels ranged from 1.55 to 15.5 times the upper limit of normal. Conclusions Extreme fluctuations of cortisol production, measured by sequential LNSC, are common in CD. In newly diagnosed disease, this may only occasionally impair diagnostic ability, whereas in most patients with recurrent/persistent disease after pituitary surgery, LNSC is frequently within the reference range, with potential to cause diagnostic problems.

Cushing’s disease and co-existing phaeochromocytoma

We report a 46 year old female who presented with a 1 year history of bruising, thin skin and weight gain (30 pounds). In addition; she reported flushing of her chest, heat intolerance, palpitations and abdominal pain. Her medical history was significant for hypertension diagnosed 2 years prior to presentation which was difficult to control. Her mother and uncle had a history of kidney cancer. On clinical examination she appeared cushingoid. Her blood pressure was elevated at 160/98 mmHg. Biochemical investigations indicated ACTH-dependent Cushing syndrome: 24 h urine free cortisol 300 lg (0–50), ACTH 119 pg/mL (8–42); midnight salivary cortisol 950 ng/dL (\100). MRI pituitary demonstrated a sellar lesion; 14 9 9 9 9 mm (Fig. 1a, arrow). She was unable to tolerate a CRH stimulation test due to a hypertensive episode during the test. To investigate the symptoms of flushing and palpitations, plasma fractionated catecholamines and metanephrines were performed and were found to be elevated; norepinephrine 822 pg/mL (80–520), epinephrine \10 pg/mL (10–200), normetanephrine 1250 pg/mL (18–101), metanephrine 34 pg/mL (12–67). CT abdomen (Fig. 1b, arrow) revealed a lipid poor right adrenal mass measuring 36 9 17 mm with corresponding Hounsfield units of 47, which was consistent with a phaeochromocytoma in view of her elevated plasma normetanephrine. She had normal serum calcium and calcitonin levels. The elevated ACTH in the presence of hypercortisolism and co-existing phaeochromocytoma raised the possibility of ectopic Cushing syndrome from an ACTH-secreting phaeochromocytoma. However, the MRI was not suggestive of pituitary hyperplasia. The patient was unable to tolerate the CRH stimulation test which would have helped to differentiate between an adrenal or pituitary aetiology of Cushing syndrome. She did not undergo a high dose dexamethasone suppression test. The patient was started on phenoxybenzamine prior to elective adrenalectomy. A robotic right trans-abdominal lateral adrenalectomy was performed without complications, histology confirmed a phaeochromocytoma. One month post-adrenalectomy plasma fractionated catecholamines and metanephrines were normal. The patient continued to be hypercortisolemic post-op. Six weeks after adrenal surgery endoscopic transsphenoidal resection of the pituitary mass was performed. The histology revealed an adenoma which was diffusely positive for ACTH, it did not stain with any other anterior pituitary hormones. The nadir cortisol and ACTH were 1.4 lg/dL and 114 pg/mL within 48 h after surgery, respectively. At 3 months post-pituitary surgery, she had normal plasma metanephrines and 24 h UFC levels with no visible residual disease on pituitary MRI. However, she underwent a second pituitary surgery for disease recurrence (2 years later) and subsequently had the remaining adrenal gland removed due to persistence of her Cushing’s disease. She remains on hydrocortisone and fludrocortisone & Philip C. Johnston pcjohnston@doctors.org.uk

Thyrotoxicosis with absence of clinical features of acromegaly in a TSH- and GH-secreting, invasive pituitary macroadenoma.

Summary A 54-year-old woman presented with bi-temporal hemianopia, palpitations, and diaphoresis. An invasive pituitary macroadenoma was discovered. The patient had biochemical evidence of secondary hyperthyroidism and GH excess; however, she did not appear to be acromegalic. Surgical removal of the pituitary mass revealed a plurihormonal TSH/GH co-secreting pituitary adenoma. TSH-secreting adenomas can co-secrete other hormones including GH, prolactin, and gonadotropins; conversely, co-secretion of TSH from a pituitary adenoma in acromegaly is infrequent. Learning points This case highlights an unusual patient with a rare TSH/GH co-secreting pituitary adenoma with absence of the clinical features of acromegaly. Plurihormonality does not always translate into the clinical features of hormonal excess. There appears to be a clinical and immunohistochemical spectrum present in plurihormonal tumors.

Cushing's disease from an ectopic parasellar adenoma

Cushings disease is a result of adrenocorticotropic hormone (ACTH)-dependent hypercortisolism, whereby the majority of cases originate from the pituitary. In rare cases, the source of excess ACTH is from an ectopic pituitary adenoma, in which the clinical and biochemical picture can often be identical to intrasellar corticotroph adenomas.1 Ectopic pituitary adenomas are defined as an adenoma that lies outside the sella and is completely distinct from the normal intrasellar pituitary gland, they can be associated with normal pituitary and in some cases, an empty sella. A 34-year-old woman presented with a 12-month history of a labile mood, weight gain, easy bruising, irregular menses and hypertension. The patient appeared cushingoid. Biochemical investigations demonstrated hypercortisolism: 24 h urine-free cortisol 520.7 mcg (4–50), …