Hypothalamic hamartoma with epilepsy: Review of endocrine comorbidity

Abstract

Summary The most common, and usually the only, endocrine disturbance in patients with hypothalamic hamartoma (HH) and epilepsy is central precocious puberty (CPP). The mechanism for CPP associated with HH may relate to ectopic generation and pulsatile release of gonadotropin-releasing hormone (GnRH) from the HH, but this remains an unproven hypothesis. Possible regulators of GnRH release that are intrinsic to HH tissue include the following: (1) glial factors (such as transforming growth factor α[TGFα) and (2) γ-aminobutyric acid (GABA)–mediated excitation. Both are known to be present in surgically-resected HH tissue, but are present in patients with and without a history of CPP, suggesting the possibility that symptoms related to HH are directly associated with the region of anatomic attachment of the HH to the hypothalamus, which determines functional network connections, rather than to differences in HH tissue expression or pathophysiology. CPP associated with HH presents with isosexual development prior to the age of 8 years in girls and 9 years in boys. It is not uncommon for CPP with HH to present in children at an earlier age in comparison to other causes of CPP, including in infancy. Surgical resection of the HH can be effective for treating CPP, but is reserved for patients with intractable epilepsy, since GnRH agonists are widely available and effective treatment. Other endocrine disturbances with HH are rare, but can include growth hormone deficiency, hypothyroidism, and adrenal insufficiency. Diabetes insipidus is commonly encountered postoperatively, but is not observed with HH prior to surgical intervention.

Hypothalamic hamartomas in adulthood: Clinical spectrum and treatment outcome—A unicenter experience

“…The hamartoma location influences the regulation of hormone release. Pedunculated HH occupying the anterior hypothalamus (Type I) may cause endocrinological disturbances, being the CPP the most frequent one, probably because of a premature pulsatile release of gonadotropin‐releasing hormone (GnRH) from the hypothalamus (Harrison et al, ; Striano & Striano, ). CPP and epilepsy coexist in up to 45% of the patients undergoing surgical treatment for epilepsy (Oehl et al, ).…”

“…Two different clinical phenotypes are described depending on the location of the hamartoma. Those HH that invade mainly the anterior hypothalamus may develop endocrinological disturbances such as central precocious puberty (CPP) and those HH affecting the posterior hypothalamus and the mammillary bodies associate drug‐resistant seizures that usually start in the early childhood as gelastic seizures (GS) (Harrison, Oatman, & Kerrigan, ; Kerrigan et al, ).However, HH have a wide clinical expression spectrum (Mullatti et al, ; Striano & Striano, ) that ranges from a few seizures with normal cognitive development to a catastrophic epileptic encephalopathy (EE) resembling a Lennox‐Gastaut‐like syndrome with cognitive impairment and severe behavioral disturbances (Cross & Spoudeas, ; Scheffer et al, ). We present the clinical features, electroencephalographic (EEG) recordings, imaging findings, and therapeutic options in a series of adult patients with epilepsy due to hypothalamic hamartoma.…”

One-Stage High-Density Focal Stereo-Array SEEG-Guided Radiofrequency Thermocoagulation for the Treatment of Pediatric Giant Hypothalamic Hamartomas

“…Hypothalamic hamartomas (HHs) are rare congenital abnormalities ( 1 ) that typically manifest as refractory epilepsy ( 2 ) and are located in the region of the tuber cinereum and the third ventricle ( 1 ). Other manifestations may include central precocious puberty and developmental retardation ( 3 – 5 ).…”

Pallister-Hall Syndrome Presenting in Adolescence

“…Endocrine manifestations of hypothalamic hamartomas consist almost exclusively of central precocious puberty (CPP) [10]. Although hypopituitarism, growth hormone deficiency, and genital hypoplasia have been described in PHS, it is not clear whether these are secondary to the hamartoma [10]. Neurologic manifestations of the hamartoma consist of gelastic seizures [11].…”