Emerging Treatments in Pituitary, Adrenal, and Neuroendocrine Disorders

Written by W. Todd Penberthy

Adult growth hormone deficiency (AGHD) means a limited quality of life, reduced bone remodeling, body fat redistribution and hyperlipidemia, and an increased predisposition to atherosclerosis, for these patients.1

Emerging therapies covering neuroendocrinology, adrenal and pituitary pathways were the focus of a series of oral posters at ENDO 2017, the Endocrine Society's 99th Annual Meeting and Expo, in Orlando, Florida, on April 1, 2017.

To date, the usual therapy for patients with AGHD is daily injections of recombinant growth hormone (rhGH), which has challenged patient adherence; high compliance can be defined as having missed 21 doses over 3 months.

Improving Administration Acceptability of GH

To address these barriers, long-lasting growth hormone preparations have been developed to provide less frequent administration: weekly with somapacitan,2 a reversible, albumin-binding GH derivative, or monthly with somavaratan, which is a long-acting rhGH.3

For both formulations,2,3 safety, tolerability, and effectiveness were found to be equivalent to previously marketed daily injection growth hormones.

“In the phase 3 adult growth hormone deficiency (AGHD) trial,2 somapacitan when administered once-weekly proved significantly more convenient and equally well tolerated, than once-daily GH injections,” said Gudmundur Johannsson, MD, professor of endocrinology at the University of Gothenburg, Sweden.

Somavaratan was shown to provide clinically significant improvements in height velocity and insulin-like growth factor-1 (IFG1) levels when administered just once a month,3 said Kevin C. Yuen, MD, MBChB, FRCP of the Swedish Neuroscience Pituitary Center, Seattle.

Evolving Treatments for Lipodystrophy  

Whereas previous leptin trials for the indication of obesity were stopped, its role in lipodystrophy has renewed interest as a possible factor in growth hormone-deficient adults, gaining Food and Drug Administration approval for generalized lipodystrophy in 2014.4

Brent S. Abel, a researcher at the National Institute of Diabetes, Digestive and Kidney Diseases, offered the potentially therapeutic use of metreleptin in positively correcting LH secretion, FSH secretion, and enhancing insulin sensitivity in patients with partial lipodystrophy.5

This has particular relevance for women who frequently are also infertile given the presence of hypogonadotropic hypogonadism and hyperandrogenism, he said.

"Six months of metreleptin therapy increased nocturnal LH secreation in patients with congential generalized or familial, partial lipodystrophy, which provides further evidence for the beneficial effect of metreleptin therapy on fertility in patients with these diseases," Rebecca J. Brown, MD, MHSc, senior author, told EndocrineWeb. Dr. Brown is the Lasker Tenure Track Investigator at the National Institute for Diabetes, Digestive and Kidney Diseases, National Institutes of Health. 

In prior studies, metreleptin treatment substantially reduced glycemic levels, triglycerides, and liver enzymes as well as demonstrated efficacy for 3 years.6 These results support metreleptin as a potential treatment for certain metabolic disorders (eg, diabetes mellitus and hypertriglyceridemia) associated with lipodystrophy.

Promising New Therapies for Pituitary Tumor’s, Cushing’s Disease

Most of the symptoms seen in Cushing’s disease (CD) are due to excessive cortisol production. Rosario Pivonello, MD, Università Federico II di Napoli, Naples, Italy, has been treating CD patients with osilodrostat, an inhibitor of the terminal reaction in cortisol biosynthesis, with promising results.7

Normal urinary free cortisol was attained within 3 weeks and maintained for up to 2.5 years in a majority of the patients, and BMI showed improvement,7 according to Dr. Pivonello. The commonly reported adverse events decreased with time, and now trials are underway to treat a larger number of patients to confirm osilodrostat as a useful therapeutic modality for CD, he said.  

Pituitary tumors are the most common intracranial tumor and have typically been characterized as benign. However, a more recent analysis8 indicates that “these should be considered as more than just an endocrine disorder,” according to Gérald Raverot, MD, PhD, professor of endocrinology at Lyon University, France.

He explained that “temozolomide treatment is the only alternative for rare pituitary carcinomas, and in some instances for pituitary tumors resistant to usual medical treatment, which are progressing despite radiation therapy.8

“It's an indication that this drug should be limited to ‘aggressive’ tumors after multidisciplinary discussion,” said Dr. Raverot, because all insulinomas highly express the GLP1 receptor.8

Accordingly, ligands for insulinoma imaging have been developed, that use either 111I or 68G conjugated to the GLP1 ligand.8

In a blind comparison of insulinoma tumor identification imaging techniques: PET/CT, SPECT/CT, and 3TMRI, PET/CT performed better than MRI imaging and GLP1R-SPECTRA in detecting benign insulinomas at lower irradiation dose and producing results in just 2.5 hours,9 according to Emanuel R. Christ MD, PhD, of University Hospital of Basel, Basel, Switzerland.

“We believe that GLP1R-PET/CT will be a useful diagnostic tool for patients in whom insulinoma is suspected,” said Dr. Christ.   



  1. Endocrine Society. The Endocrine Society Clinical Practice Guidelines on Diagnosis and Treatment of Growth Hormone Deficiency in Adults—2011 Update. J Clin Endocrinol Metab. 2011;96(6):1587-1609
  2. Johannsson G, Feldt-Rassmussen U, Hakonsson IH, et al. Convenience of the once-weekly growth hormone (GH) derivative somapacitan in adult GH deficiency (AGHD): Results from a 26-week randomized, controlled phase3 trial. Presented at: ENDO2017 in Orlando, Florida; April 1, 2017.
  3. Yuen K. Somavaratan, a Long-Acting Recombinant Human Growth Hormone (rhGH), for the Treatment of Adults with Growth Hormone Deficiency (AGHD): Results of VITAL, an Open-Label, Dose-Finding, International, Phase 2. Presented at: ENDO2017 on April 1, 2017; Orlando, Florida.
  4. Food and Drug Administration. Initial REMS approval letter. https://www.fda.gov/downloads/drugs/drugsafety/postmarketdrugsafetyinformationforpatientsandproviders/ucm388903.pdf
  5. Abel B, Sedmak C, Walter MF, et al. Long-Term Effects of Recombinant Human Leptin (Metreleptin) on Nocturnal LH Secretion in Lipodystrophy Patients. Presented at: ENDO2017 on April 1, 2017; Orlando, Florida.
  6. Chan JL, Lutz K, Cochran E, et al. Clinical effects of long-term metreleptin treatment in patients with lipodystrophy. Endocr Pract. 2011;17(6):922-32.
  7. Pivonelllo R. Osilodrostat Can Provide Control of Urinary Free Cortisol for over 2.5 Years in Patients with Cushing's Disease: Results from an Extension to the Linc-2 Study. Presented at: ENDO2017 on April 1, 2017; Orlando, Florida.
  8. Raverot  G. Temozolomide Treatment Can Improve Overall Survival in Aggressive Pituitary Tumors and Pituitary Carcinomas. Presented at: ENDO2017 on April 1, 2017; Orlando, Florida.
  9. Christ ER. Localization of Benign Insulinomas Using Glucagon-like Peptide-1 Receptor (GLP1-R) SPECT/CT and PET/CT and MRI in a Prospective Clinical Study. Presented at: ENDO2017 on April 1, 2017; Orlando, Florida.