A clinical approach to the thyrotropic axis

Chapter 10

A clinical approach to the thyrotropic axis Introduction The thyrotropic axis is the second of the two catabolic axes. Recall that its purpose is to manage adaptation and growth. Because of the diversity of these demands and the evolutionary history that resulted in this axis (The Theory of Endobiogeny, Volume 1, Chapter 8), the function of each hormone and emunctory within the axis goes far beyond vertical hypothalamic-pituitary-thyroid regulation. Understanding the similarity and divergence of the arrangement and function of the two catabolic axes helps the clinician identity areas of oversolicitation, imbalance, and regulation (Table 10.1). For example, if the corticotropic axis one notes a low adrenocorticotropin hormone (ACTH) index and elevated cortisol, and, in the thyrotropic axis elevated thyroid relaunching and thyroid index, the origin of both will be related to alpha-­sympathetic activity. Using a sympatholytic such as Lavandula angustafolia (lavender) essential oil or Passiflora incarnata (passionflower) may be sufficient to regulate both axes. However,

if the t­hyrotropic axis has multiple indexes elevated and the corticotropic axis is not deranged to a similar degree, treatment should focus primarily and alpha-­sympatholytic and thyrotropic plants that inhibit central activity. For example, in addition to lavender and passionflower, one would be wise to use Lycopus europaeus (gypsywort) and Fabiana imbricata (pichi) to inhibit thyrotropin-releasing hormone (TRH) and thyroid-stimulating hormone (TSH) and peripheral thyroid activity.1, 2 The chief metabolite of the thyrotropic axis is lipids, its chief mineral calcium. When evaluating indexes of this axis, also evaluate the lipid panel and indexes related to passive cellular permeability within the somatotropic axis. With respect to calcium, evaluate the serum calcium level, the adaptogen index, parathyroid hormone index, etc. Unlike the corticotropic axis, the thyrotropic contains within itself the means to utilize or facilitate that which it has mobilized. Table 10.2 summarizes metabolites and the thyrotropic hormones implicated.

TABLE 10.1  A comparison of the two catabolic axes in first and second loops First loop

Corticotropic

Thyrotropic

Hypothalamic

CRH

TRH

Anterior pituitary

ACTH

TSH

End-organ hormone

Cortisol

Annexal organ(s)

Liver

Thymus Parathyroid: PTH

Second loop

Corticotropic

Thyrotropic

Hypothalamic

CRH

TRH

Anterior pituitary

ACTH

TSH

End-organ hormone

Aldosterone

T3

Annexal organs

Liver, lung, kidney: Angiotensin II, renin

Skin, liver, kidney: Vitamin D

Emunctories and implicated organs

Skin, kidney, liver, gallbladder digestive tract

Liver, gallbladder, digestive tract, exocrine pancreas, endocrine pancreas, lungs

DHEA

The Theory of Endobiogeny. https://doi.org/10.1016/B978-0-12-816908-7.00010-4 © 2019 Elsevier Inc. All rights reserved.

T4

Calcitonin

145

146  The Theory of Endobiogeny

TABLE 10.2  Mobilization and utilization of metabolites by the thyrotropic hormones Mobilization Metabolite

TRH

Glucose

•

Amino acids

•

T4

Utilization PTH/D3

•

Lipids

•

Calcium

•

TSH

T3

•

•

•

•

D3

Calcitonin

•

•

• •

•

D3, vitamin D3; PTH, parathyroid hormone.

Anatomy, pathophysiology The thyrotropic axis has a notable impact on the development of ectodermal tissues, especially the nervous system, the adrenal medulla (βΣ), and immunity. The pituitary gland is an ectodermal tissue and hence this axis regulates the very foundation of endocrine management of the periphery. The thyrotropic axis is permanently linked to structural formation, structural maintenance, and functional competency of adaptation. The thyrotropic axis gives birth to βΣ, and βΣ entrains and enlivens the thyrotropic axis in turn by sensibilizing tissues to T4 activity. Adaptation syndromes, spasmophilia, neurologic disorders, and disorders of hyper- and autoimmunity are all disorders that lay within the thyrotropic axis. With respect to diseases of adaptation and adaptability, both catabolic axes are directly relaunched by αΣ. Thus, both axes are directly linked to conscious, subconscious, and physiologic perceptions of and response to aggression (The Theory of Endobiogeny, Volume 1, Chapter 12). From the evolutionary perspective, the thyrotropic axis is also closely linked to the sympathetic branch of the autonomic nervous system (ANS) because dopamine, noradrenalin, adrenaline, T4, and T3 are all derived from the amino acid tyrosine. The role of TRH in all these activities cannot be underestimated. It directly or indirectly affects all four axes. In the corticotropic axis, it fixates cortisol to its receptors. In the gonadotropic axis, it stimulates follicle-stimulating hormone (FSH) and directly affects estrogen activity. Its thyrotropic function is the classic vertical activity and stimulation of conversion of T4 to T3. TRH has a privileged thyro-­somatotropic relationship as the hypothalamic stimulator of prolactin (which also alters the impact of estrogens). In the somatotropic axis, it stimulates the release of glucagon from the endocrine pancreas with a reflexive

response by insulin. Recall its central actions as a neurohormone is related to circadian and seasonal adaptation, thought, and emotions. TRH is also a general neuromodulator. Ultimately, TRH assists in the integration of the interior and external worlds.

Clinical significance of the thyrotropic axis When evaluating the level of function of the thyrotropic axis, it is capital to understand two concepts from an endobiogenic perspective. First, a number of the symptoms attributed to hypo- and hyperfunctioning of thyroid hormones are due to central thyroid hormones (TRH, TSH), or the sensibilization of other neuroendocrine factors and not the peripheral hormones ipso facto. Second, most signs, symptoms, and disorders related to the thyrotropic axis are relative and qualitative in nature, not absolute or quantitative. Table 10.3 demonstrates the role of various aspects of the thyrotropic axis in hyperthyroidism. Table  10.4 demonstrates the various aspects of the aspect with respect to hypothyroidism.

Symptoms related to the thyrotropic axis Various symptoms can be related to the thyrotropic axis (Table 10.5).

Signs related to the thyrotropic axis There are a number of signs related to the thyrotropic axis. They can be divided into the following areas: temperament an internal mental life (Table 10.6), neurologic (Table 10.7), head, ears, eye, nose and throat (Table  10.8), thyroid and chest (Table 10.9), and miscellaneous areas (Table 10.10).

A clinical approach to the thyrotropic axis Chapter | 10  147

TABLE 10.3  Role of various aspects of the thyrotropic axis in hyperthyroidism Thyrotropic factor Factor

↑ TRH

↑ TSH, serum

Endocrine Symptom

Tremors Muscle wasting Insomnia

Exam

↑ Deep tendon reflex Eyelid flutter Clonus

Inflammation Hair loss Brain fog

↑ T4

↑ T3

Overproduced from overstimulation

Overproduction, overconversion

Heat intolerance (if insufficient conversion to T3)

Cold sensitivity

Skin temperature elevated ↑ Osteoclasty

Structural Types of hyperthyroidism Reactive

Hypercatabolic, reactive thyroid state: Asthma, spring arthritis

Fundamental

Low TSH relaunching; peripheral hyperthyroidism: hyperestrogenic (thus hyper T4), hyper beta, risk of breast cancer; psoriasis Treatment: Lycopus europaeus, Borago officinalis; if DHEA, ACTH implicated in the estrogenism: Fragaria vesca

TABLE 10.4  Role of various aspects of the thyrotropic axis in hypothyroidism Thyrotropic factor Factor

TRH insufficient

↑ TSH, serum

↑ T4

↑ T3

Endocrine

Insufficient conversion of T4 to T3

Insufficient production of T4

Anabolic predominance

Mitochondrial strain

Symptom

Repetitive dreams

Weight gain

Hair loss Thinning eyebrows Alteration in timbre of voice: low, weak, and/ or hoarse

Fatigability

Exam

Hyperestrogenism

Types of hypothyroidism Latent

Lymphocytosis; cardiac vegetations; tonsil hypertrophy; appendix hypertrophy

Entrained

Elevated TRH or PL or DA; If there is elevated GH → appeal to glucose with diminished effect of GH (from strong insulin response)

Reactive TSH compensation

Fat pad above ankles (like Kurdish pants); Cobble stoning of posterior pharynx Treatment: Avena sativa, Verbascum thapsus

TABLE 10.5  Symptoms related to the thyrotropic axis3 Category

Finding

Level

State

Brain

General mental fatigue

Thyroid

Insufficient or excessive

Dermatologic

Pruritis

Thyroid

Elevated

Psoriasis

T4

Elevated

General physical fatigue

Thyroid

Insufficient

Energy, lack of

Thyroid

Insufficient

Ear, nose, throat

Enlarged tonsils

Thyroid/TSH, serum

Insufficient/elevated

Genito-urinary

Reduction in the duration on menstruation

Thyroid

Excessive

Reduction in the volume of menstrual flow

Thyroid

Insufficient

PMS with great irritability

Thyroid

Increased

Menstrual flow heavy

Thyroid

Insufficient

Heat intolerance

T4

Hyperfunctioning

Cold sensitivity

T3

Hyperfunctioning

Constantly cold

Thyroid

Deficient in response

Weight loss despite a good appetite

Thyroid

Excessive

Weight gain

Thyroid

Insufficient, especially with elevated TSH serum and relative to global adrenal cortex activity

Insomnia with great agitation

TRH

Hyperfunctioning

Dreams animated, vivid

TRH

Hyperfunctioning

Dreams in black and white

TRH

Insufficient

Repetitive dreams

TRH

Augmented

Energy

Metabolic

Sleep

TABLE 10.6  Temperament and internal mental life3 Finding

Level

Activity

Comment

Great vivacity

Thyroid

Dynamically efficient

Goal oriented

TRH

Predominant

Relative to TSH. It indicates being flexible in conceiving various orders and methods of executing plans. It does not imply that the person has the capacity to execute, only that they can conceive of multiple ways of performing

Process-oriented

TSH

Predominant

Relative to TRH. It is a tendency to be less willing, or, less able to conceive of alternate ways of executing a series of actions that were planned in advance in a particular order

Soft, easily gives in

Thyroid

Insufficient, especially during adaptation

Evaluate for strong para, weak beta, weak TRH

Fearfulness

Thyroid

Insufficient

Correlate with hyper-TRH that attempts to relaunch peripheral thyroid activity

Anxiety and nervousness

TRH

Hyperfunctioning

Tendency; correlate with elevated central and peripheral alpha and elevated dopamine

Expansive creativity

TRH

Predominant

Relative to TSH, with complementary levels of central histamine serotonin and dopamine. This type of creativity arises seeing novel relationships through tangential association

Juxtapositional creativity

TSH

Predominant

Relative to TRH. This type of creativity arises from analytical thinking with juxtaposition of basic elements into novel relationships

Depressive tendency

Thyrotropic

Dysfunctional

Correlate with hyper-TRH if comorbidity of anxiety, with insufficient peripheral thyroid activity if flat affect or psychomotor retardation. TSH has variable effects

A clinical approach to the thyrotropic axis Chapter | 10  149

TABLE 10.7  Neurologic signs3 Part

Quality

Finding

Level

Activity

Comment

General

Startle response

Startles easily to the lightest touch or sound

TRH

Reactive

Correlate with strong beta expression

Eyelids

Flutter

Spontaneous at rest

TRH

Hyperfunctioning

Base line thought

Eyelids

Flutter

Spontaneous interacting

TRH

Hyperfunctioning

In adaptation

Glabellar tap

Postglabella tap movement

Eyelid rapid flutter

TRH

Reactive

Eye

Pupillary light reflex

Exaggerated constriction to light

TRH

Reactive

Clonus

Foot

Brisk, diffuse

TRH

Elevated

Via spinal column

Deep tendon reflex (DTR)

Tendons

Brisk, diffuse

TRH

Elevated

Via spinal column

Extremities

Arms, hands, legs

Tremors

TRH

Excessive

And dysregulated; correlate with dopamine and alpha

TABLE 10.8  Signs related to head, ears, eye, nose, and throat3 Part

Quality

Finding

Level

Activity

Comment

Body

Build

Sharp features

TSH

Predominant

Example: Sharp nose, high cheek bones, pointed chin, oval face, thin build

Voice

Quality

Weak and hoarse

Thyroid

Insufficient

T3 is generally more implicated than T4

Skin

Temperature and moisture

Cold and dry

Thyroid

Insufficient

Generalized to entire body

Nail

Thickness

Fine and breakable

Thyroid

Insufficient

Hair

Quality

Thick

Thyroid

Favorably adapted

Curly hair

TRH

Predominant

Fragile

Thyroid

Insufficient

Thin

Thyroid

Not predominant

Falls out easily

Thyroid

Insufficient

Alopecia

Thyroid

Insufficient

Or in autoimmune terrain

Arch

Convex

TRH

Predominant

Occurs when there is a strong GH and ACTH response

Pilosity

Fine

Thyroid

Strong

Thinning from hair loss at the ends

Thyroid

Diminished

Relative to historically adapted levels

Length

Long

Thyroid

Well functioning

Initiated by FSH

Curvature

Curled at ends

Thyroid

Insufficient to demand

Gonadotropic appeal to re-equilibrate thyroid to gonadotropic function

Eyebrow

Eyelashes

Structural role of TRH along with appeal to thyroid and GH; all three conditions must be present

In structural nourishment of hair

TABLE 10.8  Signs related to head, ears, eye, nose, and throat—cont’d Part

Quality

Finding

Level

Activity

Comment

Eye

Size

Large

TRH, alpha, central

Strong

More predominant in children and women with anxiety tendency

Small

Thyroid

Insufficient

Inability to readjust peripheral thyroid activity during fetal development

Tonsils

Size

Hypertrophy

Thyroid

Insufficient responsiveness to TSH

Reflects a latent thyroid insufficiency

Pharynx

Deformity

Cobble stoning

Thyroid

Insufficient responsiveness to TSH

Elevated TSH to compensate for latent thyroid insufficiency

TABLE 10.9  Signs related to the thyroid gland and chest3 Part

Quality

Finding

Level

Activity

Comment

Thyroid

Volume

Increased

Thyroid

Augmented

Consistency

Nodules

Thyroid

Oversolicited

Consistency

Goiter

Thyroid

Insufficient

Clavicle, bilateral

Proximal

Pain on palpation

Sternum

Orientation

Convex sternum

PTH

Elevated

Correlate with GH

Breasts

Asymmetry

Left > right

TSH

Predominant

Instructure, in response to the basic influence of LH on laterality

Heart

Rate

Heart rate rapid

Thyroid

Augmented

May be absolutely elevated or augmented by TRH and/or cortisol

Finding

Level

Activity

TSH demand greater than T4 response

Thyroid gland congestion from oversolicited

TABLE 10.10  Others signs by region3 Part

Quality

Comment

Anterior projection of organs represents the current anatomical congestion and/or state of dysfunction Colon

Transverse, distal, left

Pain on palpation

TSH

Strong

Oversolicitation of thyroid and splenic flexure for nutrient reuptake

Colon

Transverse, distal, right

Pain on palpation

TRH

Predominance

Relative to TSH

Posterior projection of organs represents chronic congestion and/or state of dysfunction T4, left

Para spinal, 2.5 cm lateral

Pain on palpation

TRH

Scapula, right

Inferior-medial, T7-T8

Pain on palpation

FSH, TRH

Congestion, colon

Scapula, left

Inferior-medial, T7-T8

Pain on palpation

TSH, PL

Congestion, colon

General

Extremities

Lymphatic congestion

Thyroid

Latent hypothyroidism

Palm

Central

Erythematous

Thyroid

Strong

Oversolicitation of exocrine pancreas

TRH role implicated; direct interpretation: Congestion, lung, bronchial involvement

A clinical approach to the thyrotropic axis Chapter | 10  151

TABLE 10.10  Others signs by region—cont’d Part

Quality

Finding

Level

Activity

Comment

Leg

Medial to ankle, bilateral

Adiposity

TSH

Elevated

Compensated hypothyroidism

Leg

Proximal tibia, most medial aspect

Pain on palpation

T4

Diminished efficiency

LH implicated in strong TSH, pain L > R on exam

Leg

Proximal tibia, most medial aspect

Pain on palpation

TSH

Strong

LH more easily disturbed than FSH by strong TSH, pain L > R on exam

Ankle

Superior to ankle

Fat pad

TSH

Reactive

Compensation attempt for weak T4

A discussion of key thyrotropic indexes of the biology of functions When approaching an evaluation of the thyrotropic indexes, first review quantitative biomarker measurements: serum TSH, free T4, free T3, thyroid antibodies, etc. This information will contextualize the interpretation of indexes, especially since serum TSH is used to calculate a number of indexes. What is presented here is not comprehensive. It is a discussion of key indexes for students working with the elementary

concepts of endobiogeny. The indexes are d­ ivided into groups based on the area of origin and area of action that the indexes represent. It is arbitrary and there are some overlaps that are not presented to avoid redundancy. Conceptually, we have grouped the indexes as ­follows: ­central indexes with peripheral impact (Table  10.11; Fig.  10.1), radial gonado-­ thyrotropic (Table 10.12), those evaluating the thyroid gland and its threshold of response (Table 10.13), and, parathyroid and bone indexes (Table 10.14).

TABLE 10.11  Central thyrotropic indexes with peripheral impact Relationship Index

Definition

Import

Direct

Thyroid relaunching

It measures the level of reactivation of the thyrotropic axis by the locus ceruleus (Fig. 10.1)

It witnesses the degree of disadaptation of the organism, implicating the solicitation of TRH for central and/or peripheral activity and all that that implies

Thyroid relaunching corrected

It measures the endogenous part of solicitation of the thyrotropic axis by the locus ceruleus. By extension, it indicates the level of endogenous disadaptation of the organism (Fig. 10.1)

It witnesses the degree of disadaptation arising specifically from endogenous causes of disadaptation

Thyroid relaunching

TRH/TSH

It measures the relative level of tissular activity of TRH in relation to that of TSH

Indirectly it evaluates the relative part of congestion vs hyperplasia in anabolic adaptation, the relative part of nutrition vs metabolic production, the relative part of neuroendocrine vs organo-metabolic adaptation, and the relative part of the elaboration of potential vs structural realization, and thus of the imaginary relative to the material realization

Amylosis index, demyelination index

Inverse

Correlations Adaptation index, genito-thyroid, beta-MSH/alphaMSH Adaptation index, genito-thyroid, beta-MSH/alphaMSH

Adenosis index, serum TSH

Estrogen index, organotissular estrogen yield index, prolactin index

152  The Theory of Endobiogeny

FIG. 10.1  Thyroid relaunching and thyroid relaunching corrected indexes. Center: the locus ceruleus, in the brain stem, is the origin of noradrenalin (NA), the neurotransmitter of alpha-sympathetic. The thyroid relaunching index evaluates the degree to which alpha stimulates TRH in the parvoventricular nucleus of the hypothalamus. TRH relaunches thyroid activity (left). The thyroid relaunching index corrected corrects the basic evaluation for the degree that this occurs due to endogenous threats, be they real or perceived, mental or emotional aggressions. In this example, the limbic area (right), stimulates alpha in the locus ceruleus, which then stimulates TRH and relaunches the thyroid. (© 2015 Systems Biology Research Group.)

TABLE 10.12  Radial gonado-thyrotropic index Relationship Index

Definition

Import

Direct

Genito-thyroid

It measures the part played by the gonads in the appeal to and response by both metabolic and endocrine thyroid activity in the functional adaptation of structure

High: Thyroid activity is efficient relative to the estrogen demand. Favors inflammation and autoimmunity Low: TSH is not able to adapt the thyroid relative to the degree of estrogen demand. Favors hyperimmunity

Cortisol

Inverse

Correlations Adaptation index, cortisol index, corrected estrogen index IL-1, thyroid index, thyroid yield

TABLE 10.13  Indexes evaluating the thyroid gland and its activity Relationship Index

Definition

Import

Direct

Inverse

Correlations

Thyroid index

It measures the effective metabolic activity of peripheral thyroid hormones

High: Thyroid metabolic activity is elevated without conclusion regarding the degree of solicitation, rate of response or requirements of the organism Low: Thyroid metabolic activity is diminished without conclusion to the degree of solicitation, rate of response or requirements of the organism

LDH

CK

Genito-thyroid, thyroid yield, metabolic yield

Thyroid yield

It measures the relative part of the thyroid’s metabolic contribution in comparison with the level pituitary stimulation

High: The thyroid is easily relaunched when its metabolic effects decline Low: There is a delay in the readaptation of thyroid metabolic activity by the pituitary

Thyroid index

Serum TSH

Genito-thyroid, thyroid yield, metabolic yield

A clinical approach to the thyrotropic axis Chapter | 10  153

TABLE 10.14  Parathyroid and bone indexes Relationship Index

Definition

Import

Direct

Inverse

Correlations

Para-thyroid hormone index (PTH)

It measures the endocrinometabolic activity of PTH

High: There is a prolonged appeal to PTH to solicit bone for adaptation due to the inefficiency of thyroid activity in regulating cellular respiration and/ or the efficiency of thyroid response to stimulation Low: The inverse holds true

Serum calcium

Thyroid metabolic index

Bone remodeling

Bone remodeling

It measures bone remodeling activity and the extent of bone impairment. It also bears witness to the general level of metabolism, and specifically to its adaptation activity

High: The bone is being solicited in its turnover activity to participate in adaptation as a source of calcium for adaptation and osteocalcin for metabolism Low: Favors a more efficient peripheral metabolic activity that does not require a strong appeal to bone

Serum TSH

Estrogen activity

PTH, adrenal cortex, estrogen index, corrected estrogen index

References 1. Duraffourd C, Lapraz JC. Traité de Phytothérapie Clinique: Médecine et Endobiogénie. Paris: Masson; 2002. 2. Lapraz  JC, Carillon  A, Charrié  J-C, et  al. Plantes Médicinales: Phytothérapie Clinique Intégrative Et Médecine Endobiogénique. Paris: Lavoisier; 2017.

3. Lapraz J-C, Clairemont de Tonnerre M-L. La Médecine Personnalisée: Retrouver Et Garder La Santé. Paris: Odile Jacob; 2012.