ACTH test after adenomectomy may accurately predict Cushing’s disease remission

A plasma adrenocorticotropic hormone suppression test performed shortly after surgical adenomectomy may accurately predict both short- and long-term remission of Cushing’s disease, according to research published in Pituitary.

“Cushing’s disease is caused by hypersecretion of adrenocorticotropic hormone (ACTH) by a pituitary adenoma, resulting in hypercortisolism,” Erik Uvelius, MD, of the department of clinical sciences, Skåne University Hospital, Lund University, Sweden, and colleagues wrote in the study background. “Surgical adenomectomy is the first line of treatment. Postoperative remission is reported in 43% to 95% of cases depending on factors such as adenoma size, finding of pituitary adenoma on preoperative MRI and surgeons’ experience. However, there is no consensus on what laboratory assays and biochemical thresholds should be used in determining or predicting remission over time.”

In the study, the researchers retrospectively gathered data from medical records of 28 patients who presented with Cushing’s disease to Skåne University Hospital between November 1998 and December 2011, undergoing 45 transsphenoidal adenomectomies.

On postoperative days 2 and 3, oral betamethasone was administered (1 mg at 8 a.m., 0.5 mg at 2 p.m., and 0.5 mg at 8 p.m.). Researchers assessed plasma cortisol and plasma ACTH before betamethasone administration and again at 24 and 48 hours, and measured 24-urinary free cortisol on postoperative day 3.

At 3 months postoperatively and then annually, plasma concentrations of morning cortisol and ACTH along with urinary-free cortisol and/or a low-dose dexamethasone suppression test were evaluated at the endocrinologists’ discretion. The researchers defined remission as lessening of clinical signs and symptoms of hypercortisolism, as well as laboratory confirmation through the various tests.

The researchers used Youden’s index to establish the cutoff with the highest sensitivity and specificity in predicting remission over the short term (3 months) and long term (5 years or more). Clinical accuracy of the different tests was illustrated through the area under curve.

The study population consisted of mainly women (71%), with a median age of 49.5 years. No significant disparities were seen in age, sex or surgical technique between patients who underwent a primary procedure and those who underwent reoperation. Two of the patients were diagnosed with pituitary carcinoma and 11 had a macroadenoma. ACTH positivity was identified in all adenomas and pathologists confirmed two cases of ACTH-producing carcinomas.

Of the 28 patients, 12 (43%) demonstrated long-term remission at last follow-up. Three patients were not deemed in remission after primary surgery but were not considered eligible for additional surgical intervention, whereas 13 patients underwent 17 reoperations to address remaining disease or recurrence. Four patients demonstrated long-term remission after a second or third procedure, equaling 16 patients (57%) achieving long-term remission, according to the researchers.

The researchers found that both short- and long-term remission were most effectively predicted through plasma cortisol after 24 and 48 hours with betamethasone. A short-term remission cutoff of 107 nmol/L was predicted with a sensitivity of 0.85, specificity of 0.94 and a positive predictive value of 0.96 and AUC of 0.92 (95% CI, 0.85-1). A long-term remission cutoff of 49 nmol/L was predicted with a sensitivity of 0.94, specificity of 0.93, positive predictive value of 0.88 and AUC of 0.98 (95% CI, 0.95-1). This cutoff was close to the suppression cutoff for the diagnosis of Cushing’s disease, 50 nmol/L. The cutoff of 25 nmol/L showed that the use of such a strict suppression cutoff would cause a low level of true positives and a higher occurrence of false negatives, according to the researchers.

“A 48 h 2 mg/day betamethasone suppression test day 2 and 3 after transsphenoidal surgery of Cushing’s disease could safely predict short- and long-term remission with high accuracy,” the researchers wrote. “Plasma cortisol after 24 hours of suppression showed the best accuracy in predicting 5 years’ remission. Until consensus on remission criteria, it is still the endocrinologists’ combined assessment that defines remission.” – by Jennifer Byrne

DisclosuresThe authors report no relevant financial disclosures.

From https://www.healio.com/endocrinology/neuroendocrinology/news/in-the-journals/%7B0fdfb7b0-e418-4b53-b59d-1ffa3f7b8cd3%7D/acth-test-after-adenomectomy-may-accurately-predict-cushings-disease-remission

Pregnant Women with Hypertension and Hypercortisolism May Have Cushing’s

Pregnant woman with hypertension and significant signs of hypercortisolism (high cortisol levels) may have Cushing’s disease, according to a new case report.

The report, titled “A Case of Cushing’s Syndrome in Pregnancy,” was published in the Iranian Journal of Medical Sciences.

While Cushing’s rarely occurs in women during pregnancy, high cortisol levels can lead to major complications for both the mother and the fetus, such as premature birth and high fetal mortality.

However, it can be difficult to diagnose pathological hypercortisolism in these women as the symptoms might resemble other diseases that commonly occur during pregnancy, such as preeclampsia (high blood pressure during pregnancy) and gestational diabetes.

Unfortunately, there are no effective long-term medical therapies for Cushing’s. The most definitive therapy is the surgical removal of the pituitary or adrenal adenoma, if that is the case of hypercortisolism.

The case report details that a 29-year old women in the 27th week of pregnancy presented to the Ghaem Hospital clinic in Mashhad, Iran, with edema, weakness, and hypertension. Her symptoms also included truncal obesity, moon face (her face had a rounded appearance), purple steria on her upper and lower limbs and abdomen, excessive edema, and wet skin.

At first, she was hospitalized for suspected preeclampsia, but the diagnosis was later excluded.

The patient’s hormonal profile showed high levels of 24-hour urine cortisol. There were also low levels of adrenocorticotropic hormone (ACTH), which results from a negative feedback due to excessive cortisol. However, plasma cortisol is generally elevated during pregnancy, and therefore may not be the best method for diagnosis.

An abdominal ultrasonography revealed a well-defined mass in the right adrenal gland.

While hospitalized, the patient experienced two crises of blood pressure, and while preeclampsia was ruled out, the physicians could find no more plausible explanation than eclampsia (the onset of seizures in a women with preeclampsia).

Since eclampsia was suspected, the physicians terminated the pregnancy at 28th week of gestation using misoprostol. The woman delivered a male infant weighing 1.94 pounds.

Two days after birth, the physicians conducted a computed tomography (CT) scan and again found a mass in the right adrenal gland.

As a result, the patient underwent a laparoscopic right adrenalectomy to remove the mass one week after giving birth. The patient’s blood pressure normalized and cortisol levels declined. Her condition remained stable after surgery.

“Cushing’s syndrome should be considered in hypertensive pregnant patients with remarkable signs of hypercortisolism,” the researchers concluded. “The best results would be achieved through a collaboration between obstetricians, endocrinologists, and surgeons.”

From https://cushingsdiseasenews.com/2017/12/19/pregnant-women-hypertension-hypercortisolism-may-have-cushings-disease/

Delayed complications after transsphenoidal surgery for pituitary adenomas

World Neurosurg. 2017 Oct 5. pii: S1878-8750(17)31710-2. doi: 10.1016/j.wneu.2017.09.192. [Epub ahead of print]

Abstract

Perioperative complications after transsphenoidal surgery for pituitary adenomas have been well documented in the literature; however, some complications can occur in a delayed fashion postoperatively and reports are sparse about their occurrence, management, and outcome.

Here, we describe delayed complications after transsphenoidal surgery and discuss the incidence, temporality from the surgery, and management of these complications based on the findings of studies that reported delayed postoperative epistaxis, delayed postoperative cavernous carotid pseudoaneurysm formation and rupture, vasospasm, delayed symptomatic hyponatremia (DSH), hypopituitarism, hydrocephalus, and sinonasal complications.

Our findings from this review revealed an incidence of 0.6-3.3% for delayed postoperative epistaxis at 1-3 weeks postoperatively, 18 reported cases of delayed carotid artery pseudoaneurysm formation at 2 days to 10 years postoperatively, 30 reported cases for postoperative vasospasm occurring 8 days postoperatively, a 3.6-19.8% rate of DSH at 4-7 days postoperatively, a 3.1% rate of new-onset hypopituitarism at 2 months postoperatively, and a 0.4-5.8% rate of hydrocephalus within 2.2 months postoperatively.

Sinonasal complications are commonly reported after transsphenoidal surgery, but spontaneous resolutions within 3-12 months have been reported. Although the incidence of some of these complications is low, providing preoperative counseling to patients with pituitary tumors regarding these delayed complications and proper postoperative follow-up planning is an important part of treatment planning.

KEYWORDS:

carotid pseudoaneurysm; cerebrospinal fluid leak; delayed complications; epistaxis; hydrocephalus; hyponatremia; hypopituitarism; pituitary; sinonasal complication; transsphenoidal surgery; tumor

Study Highlights Importance of Clinical Follow-Up in Cushing’s Patients After Adenoma Removal

A rare case of Cushing’s syndrome (CS) in a 17-year-old patient with multiple pituitary adenomas highlights the importance of clinical follow-up in order to determine the best treatment options for patients.

The study, “A rare case of multiple pituitary adenomas in an adolescent Cushing disease presenting as a vertebral compression fracture,” was published in the journal Annals of Pediatric Endocrinology and Metabolism

CS is a very rare disease with an incidence of 0.7-2.4 cases per million, per year. It is caused by exposure to very high levels of the hormone cortisol. In children, the most common symptom is weight gain without height gain. In some rare cases, tumors known as multiple pituitary adenomas (MPAs) appear, and patients have elevated levels of adrenocorticotropic hormone (ACTH). Surgical removal through transsphenoidal surgery (TSS) is considered the best treatment, and the first TSS has a success rate of more than 90%.

However, since 15% of patients have a recurrence, ongoing monitoring and follow-up after TSS are important. The importance of this follow-up care is highlighted in a recent case report.

The study described the case of a 17-year-old male adolescent who was 149.5 cm tall (4’9″) and weighed 63.6 kg (140 lbs). The patient was referred to a hospital for the evaluation of a vertebral compression fracture and obesity. Over four years, the patient gained 23 kg (51 lbs) without an increase in height. Despite showing many of the features of CS, this patient had not been previously diagnosed with CS.

He had high levels of ACTH and cortisol, and an MRI suggested the presence of an 8-mm (0.8 cm) micro-adenoma. After TSS, the patient’s morning ACTH and cortisol levels were reduced, and a persistent headache had improved. But there was no reduction in weight.

Three months after the TSS, the patient’s body mass index did not show improvement, and both cortisol and ACTH levels were elevated again. MRI revealed a new 9 mm (0.9 cm) micro-adenoma, which was removed with a second TSS. However, cortisol and ACHT remained elevated after the second surgery, with no evidence of a pituitary tumor in MRI scans.

Researchers recommended additional options, such as total removal of the pituitary gland, radiotherapy, or removal of both adrenal glands, options that the patient and his family declined. He continued to receive treatment for osteoporosis, hypertension, and increased lipid levels.

“In conclusion, we reported the clinical course of Cushing disease with 2 distinct pituitary adenomas. Since there is no consensus as to the best treatment for relapsing or persistent Cushing disease and since only a few cases of MPA among pediatric Cushing disease have been reported, a close followup of tumor status, severity of hypercortisolism, and patients’ perspectives are the major parameters used to determine the best treatment option for each patient. In addition, early recognition and diagnosis of pediatric Cushing disease would lead to earlier recovery, improved growth, and better quality of life,” the researchers wrote.

From https://cushingsdiseasenews.com/2017/10/27/cushings-disease-rare-case-report-highlights-importance-early-diagnosis-follow-up-care/

A Retrospective Review of 34 Cases of Pediatric Pituitary Adenoma

Abstract

Purpose

The purpose of this paper is to study invasiveness, tumor features and clinical symptoms of pediatric pituitary adenoma, and to discuss some inconclusive results in prior studies.

Methods

We retrospectively reviewed 34 cases of children (<20 year-old) who were pathologically diagnosed with pituitary adenoma and surgically treated from 2010 to 2017. Data of general information, clinical symptoms, invasive behaviors, surgery approaches, and tumor features were collected and analyzed.

Results

Sixteen boys and 18 girls aged from 12 to 19 years old were included. Prolactinoma was most suffered, followed by GH-, none- and ACTH-secreting pituitary adenoma. Invasive behaviors were observed frequently and suprasellar extensions were most found. Macroadenoma account 70% of all cases. Meanwhile, unlike prior studies, a significant raise of incidence on invasive tumor and pituitary adenoma apoplexy were observed. Craniotomy and transsphenoidal surgery were both applied with zero mortality. Nine cases occurred with transient hypopituitarism and diabetes insipidus. Three cases of tumor recurrence received secondary surgery or radiotherapy.

Conclusions

Invasive behaviors were more frequent than previous prediction. Craniotomy is worth considering for total tumor removal. Pituitary adenoma apoplexy needs further studies since its different features between children and adults in present study. Specialized care and teamwork of neurosurgeons, pediatricians, and endocrinologists are important.

Keywords

Pediatric pituitary adenoma Invasion Pituitary apoplexy Transsphenoidal surgery 

%d bloggers like this: