Rare Malignant Tumor of Adrenal Gland Led to Cushing’s, Girl’s Death

While adrenocortical carcinoma — a malignant tumor of the adrenal gland — appears only rarely in children, the tumor may cause secondary Cushing’s syndrome in these patients, a new case report shows.

Early diagnosis of the causes of Cushing’s syndrome could improve the prognosis of these children, researchers say.

The study, “Cushing Syndrome Revealing an Adrenocortical Carcinoma,” was published in the Open Journal of Pediatrics.

Adrenocortical carcinoma is a malignant tumor that develops in the cortex of the adrenal gland. It usually is identified by increased amounts of hormones that are produced by the adrenal glands, like cortisol.

This tumor type is very rare in children, representing fewer than two in every 1,000 pediatric tumors.

Researchers at the University Hospital Center Souro Sanou, in Burquina Faso (West Africa), described the case of a 10-year-old girl who developed this rare cancer.

The patient’s first symptoms were loss of consciousness and recurrent seizures without fever. The patient also had experienced excessive weight gain in the preceding months. At admission she was in a light state of coma and showed obesity in the face and trunk.

An initial analysis of blood, urine, and cerebrospinal fluid failed to detect any alterations, with no diabetes, kidney damage, or infection identified. And, even though no lesions or alteration were seen in the pituitary gland region, brain swelling was detected.

While in the hospital, the patient’s condition continued to deteriorate. She developed fever and difficulty speaking, while showing persistent seizures.

In the absence of a diagnosis, physicians focused on the safeguard of major vital function, control of seizures, and administration of large-spectrum antibiotics. Her condition improved slightly, regaining consciousness and control of seizures.

One month later, however, the patient developed symptoms that are commonly associated with increased levels of cortisol and male sex hormones, including obesity and early development of pubic hair.

After confirming high cortisol levels, physicians examined the patient’s abdominal region,  which revealed a tumor in the left adrenal gland.

The patient received a ketoconazole treatment and a surgery to remove the tumor was planned. But her condition worsened, with development of malignant hypertension and convulsive illness, which led to her death before the tumor was removed.

“The delay in the diagnosis and the insufficiency of the therapeutic means darken the prognosis in our context,” the researchers wrote.

“[Adrenocortical carcinoma] diagnosis should be considered in presence of virilization and early signs of puberty,” the researchers suggested. “Early diagnosis and multidisciplinary management of adrenocortical carcinoma could improve the prognosis in children.”

From https://cushingsdiseasenews.com/2018/05/04/rare-malignant-tumor-adrenal-gland-caused-cushings-case-report/

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 

Pediatric Endocrine Society Provides Guidance for Growth Hormone Use in Pediatric Patients

HealthDay News—Use of growth hormone in children and adolescents should be considered carefully, with assessment of the risks and benefits necessary for each patient, according to guidelines published in the January issue of Hormone Research in Paediatrics.

Adda Grimberg, MD, from the Perelman School of Medicine at the University of Pennsylvania in Philadelphia, and colleagues updated guidelines on the use of growth hormone, focusing on idiopathic short stature (ISS), GH deficiency (GHD), and primary insulin-like growth factor-I (IGF-I) deficiency (PIGFD). The guidelines were written on behalf of the Pediatric Endocrine Society.

The researchers recommend use of growth hormone for children and adolescents with GHD. Prospective recipients of growth hormone treatment should receive guidance regarding potential adverse effects and should be monitored for these effects. Parents and clinicians should take a shared decision-making approach to treating patients with ISS, and assess the physical and physiological burdens for the child, while considering the risks and benefits of treatment.Follow-up assessment of benefit and psychosocial impact should be conducted at 12 months after initiation and dose optimization of GH. IGF-I therapy is recommended for patients with severe PIGFD. Diagnosis of PIGFD/GH insensitivity syndrome should be based on a combination of factors that fall into four stages.

Physicians with expertise in managing endocrine disorders in children should provide consultation for evaluation of GHD-ISS-PIGFD and manage treatment.

“The taskforce suggests that the recommendations be applied in clinical practice with consideration of the evolving literature and the risks and benefits to each individual patient,” the authors write. “In many instances, careful review highlights areas that need further research.”

Several authors disclosed financial ties to the pharmaceutical industry.

Reference

Grimberg A, DiVall SA, Polychronakos C, et al; on behalf of the Drug and Therapeutics Committee of the Pediatric Endocrine Society. Guidelines for growth hormone and insulin-like growth factor-I treatment in children and adolescents: growth hormone deficiency, idiopathic short stature, and primary insulin-like growth factor-I deficiency. Horm Res Paediatr. 2016;86(6):361-397. doi: 10.1159/000452150

 From http://www.endocrinologyadvisor.com/adrenal/growth-hormone-use-in-pediatric-patients/article/634909/

Cortisol: Chronic Stress Increases the Risk of Early Puberty

Scientists are trying to understand how childhood adversity affects puberty, but linking the two is difficult. Hair cortisol concentration (HCC) is a potentially useful biological marker of chronic stress. However, previous studies were unable to link childhood adversity to puberty in boys.

Research published in JAMA Pediatrics by Ying Sun and colleagues examined HCC and pubertal development in 1263 elementary school-aged children (age range 6.4 – 9.9 years) in China. Cortisol was extracted from hair samples and measured using a commercially available cortisol test kit.

For girls, breast development was assessed by the same pediatric endocrinologist using Breast Tanner stages, a scale of physical development. For boys, a Prader orchidometer was used to estimate testicular volume. The study found no difference in cortisol levels between boys and girls. Early breast development was significantly higher for girls with the HCC levels in the third and fourth quartile compared to those with lower HCC levels. Overall, the investigators found a 2.5-fold increase in the risk of early breast development in girls in the highest quartile of HCC compared to those in the lowest quartile.

Similarly, testicular volume in boys was significantly correlated (p< .001) with HCC, those with higher levels of HCC had larger mean testicular volumes. A 0.12-milliliter increase in testicular volume was observed with each quartile increase in HCC in boys.

This is the first study to measure the cortisol level in hair of children in relation to puberty. Scientists hope that additional studies will help us better understand the timing of puberty and how chronic stress increases the risk of early puberty.

Written By: Cindi A. Hoover, Ph.D.

From https://www.medicalnewsbulletin.com/chronic-stress-increases-risk-early-puberty/

Cushing’s appears to begin its cardiovascular effects during childhood

– Cushing’s disease may begin to exert its harmful cardiovascular effects quite early, a small pediatric study has found.

Children as young as 6 years old with the disorder already may show signs of cardiovascular remodeling, with stiffer aortas and higher aortic pulse-wave velocity than do age-matched controls, Hailey Blain and Maya Lodish, MD, said at the annual meeting of the Endocrine Society.

“The study, which included 10 patients, is small, but we continue to add new patients,” said Dr. Lodish, director of the pediatric endocrinology fellowship program at the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Ten more children are being added to the cohort now, and she and Ms. Blain, a former research fellow at NIH, intend to grow the group and follow patients longitudinally.

Cushing’s disease has long been linked with increased cardiovascular risk in adults, but the study by Dr. Lodish and Ms. Blain is one of the first to examine the link in children. Their findings suggest that early cardiovascular risk factor management should be a routine part of these patients’ care, Dr. Lodish said in an interview.

“It’s very important to make sure that there is recognition of the cardiovascular risk factors that go along with this disease. Elevated levels of cholesterol, hypertension, and other risk factors that are in these individuals should be ameliorated as soon as possible from an early age and, most importantly, physicians should be diagnosing and treating children early, once they are identified as having Cushing’s disease. And, given that we are not sure whether these changes are reversible, we need to make sure these children are followed very closely.”

Indeed, Dr. Lodish has reason to believe that the changes may be long lasting or even permanent.

“We are looking at these children longitudinally and have 3-year data on some patients already. We want to see if they return to normal pulse wave velocity after surgical cure, or whether this is permanent remodeling. There is an implication already that it may be in a subset of individuals,” she said, citing her own 2009 study on hypertension in pediatric Cushing’s patients. “We looked at blood pressure at presentation, after surgical cure, and 1 year later. A significant portion of the kids still had hypertension at 1 year. This leads us to wonder if they will continue to be at risk for cardiovascular morbidity as adults.”

Ms. Blaine, an undergraduate at Bowdoin College, Brunswick, Maine, worked on the study during a summer internship with Dr. Lodish and presented its results in a poster forum during meeting. She examined two indicators of cardiovascular remodeling – aortic pulse wave velocity and aortic distensibility – in 10 patients who were a mean of 13 years old. All of the children came to NIH for diagnosis and treatment of Cushing’s; as part of that, all underwent a cardiac MRI.

The patients had a mean 2.5-year history of Cushing’s disease Their mean midnight cortisol level was 18.8 mcg/dL and mean plasma adrenocorticotropic hormone level, 77.3 pg/mL. Five patients were taking antihypertensive medications. Low- and high-density lipoprotein levels were acceptable in all patients.

The cardiovascular measures were compared to an age-matched historical control group. In this comparison, patients had significantly higher pulse wave velocity compared with controls (mean 4 vs. 3.4 m/s). Pulse wave velocity positively correlated with both midnight plasma cortisol and 24-hour urinary free cortisol collections. In the three patients with long-term follow-up after surgical cure of Cushing’s, the pulse wave velocity did not improve, either at 6 months or 1 year after surgery. This finding echoes those of Dr. Lodish’s 2009 paper, suggesting that once cardiovascular remodeling sets in, the changes may be long lasting.

“The link between Cushing’s and cardiovascular remodeling is related to the other things that go along with the disease,” Dr. Lodish said. “The hypertension, the adiposity, and the high cholesterol all may contribute to arterial rigidity. It’s also thought to be due to an increase in connective tissue. The bioelastic function of the aorta may be affected by having Cushing’s.”

That connection also suggests that certain antihypertensives may be more beneficial to patients with Cushing’s disease, she added. “It might have an implication in what blood pressure drug you use. Angiotensin-converting enzyme inhibitors increase vascular distensibility and inhibit collagen formation and fibrosis. It is a pilot study and needs longitudinal follow up and additional patient accrual, however, finding signs of cardiovascular remodeling in young children with Cushing’s is intriguing and deserves further study.”

Neither Ms. Blain nor Dr. Lodish had any financial disclosures.

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